MRE11 encodes the nuclease subunit of the conserved Mre11-Rad50-Xrs2 (MRX) complex of budding yeast. Mre11 is a Mn2+-dependent metallophosphoesterase-family nuclease. Its N-terminal nuclease domain has single-stranded DNA endonuclease, Sae2-stimulated double-stranded DNA endonuclease and 3'-5' DNA exonuclease activities. Its C-terminal region binds DNA and meiotic proteins. Mre11 is the binding core that bridges Rad50 and Xrs2, and Xrs2 is required for its nuclear import. At DNA double-strand breaks, MRX recognises and tethers DNA ends. When ends are blocked by proteins such as Spo11 or Ku, Mre11 nicks the 5'-terminated strand internally and resects back toward the end. This initiates resection for homologous recombination, which Exo1 and Sgs1-Dna2 then extend. Through nuclease-independent, structural functions of the complex, Mre11 is also needed for nonhomologous end joining, telomere length maintenance, Tel1-dependent DNA damage signaling and, in meiosis, Spo11-dependent DSB formation. Minor roles have been reported in mitochondrial DNA repair, base excision repair and trinucleotide repeat expansion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000014 single-stranded DNA endonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: Single-stranded DNA endonuclease activity, propagated from the family-root PAINT node PTN000015644. Reason: This function is directly demonstrated for purified S. cerevisiae Mre11. Single-stranded endonuclease activity is lost in the D56N and H125N phosphoesterase-motif mutants (PMID:9858579). It also cleaves the 3' ssDNA tail of hairpin substrates (PMID:11454871). The family-root placement is consistent with the conserved phosphoesterase motifs shared by all SF1 and SF4 members. Supporting Evidence: PMID:9858579 the purified Mre11 protein was found to have single-stranded endonuclease activity PMID:11454871 Mre11 is capable of cleaving hairpins and the 3' single-stranded DNA tail file:yeast/MRE11/MRE11-uniprot.txt Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity |
| GO:0000723 telomere maintenance | IBA GO_REF:0000033 | ACCEPT | Summary: Telomere maintenance (IBA; S. cerevisiae MRE11 is among the donors). Reason: mre11 null mutants have short telomeres (PMID:9501103, PMID:9858579), and MRX oligomerization is required for telomere maintenance (PMID:35501303). Nuclease-dead alleles keep normal telomeres (PMID:9858579), so this role is structural: MRX loads at telomeres and recruits the checkpoint kinases. Supporting Evidence: PMID:9501103 RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance PMID:9858579 Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant PMID:35501303 We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo |
| GO:0000723 telomere maintenance | IMP PMID:9501103 Components of the Ku-dependent non-homologous end-joining pa... | ACCEPT | Summary: Telomere maintenance; mre11 mutants have shortened telomeres. Reason: Boulton & Jackson showed that RAD50, MRE11 and XRS2 are required for telomere length maintenance (PMID:9501103). This was confirmed by later work (PMID:9858579). Supporting Evidence: PMID:9501103 RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance PMID:9858579 Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: DSB repair via homologous recombination (IBA; S. cerevisiae MRE11 is a donor). Reason: Mre11 initiates HR by endonucleolytic nicking and 3'->5' resection of 5' strands (PMID:22002605, PMID:25231868). It is also required for sister-chromatid recombination of replication-born DSBs (PMID:23254329). This is the core process for the nuclease. Supporting Evidence: PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex PMID:23254329 We provide evidence that MRX, particularly its Mre11 nuclease activity, and Sae2 are required for SCR-mediated repair of DSBs |
| GO:0000727 double-strand break repair via break-induced replication | IGI PMID:17321803 Mre11 and Ku regulation of double-strand break repair by gen... | KEEP AS NON CORE | Summary: Break-induced replication. Reason: Krishna et al. conclude that Mre11 functions in Rad51-independent BIR, which is suppressed by yku70 deletion (PMID:17321803). BIR frequency actually increased in mre11 mutants, so the relationship is regulatory or pathway-choice rather than a catalytic step. Kept as non-core. Supporting Evidence: PMID:17321803 These results indicate that Mre11 functions in Rad51-independent BIR, and that Ku functions in Rad51-dependent BIR |
| GO:0000727 double-strand break repair via break-induced replication | IMP PMID:17321803 Mre11 and Ku regulation of double-strand break repair by gen... | KEEP AS NON CORE | Summary: Break-induced replication. Reason: Krishna et al. conclude that Mre11 functions in Rad51-independent BIR, which is suppressed by yku70 deletion (PMID:17321803). BIR frequency actually increased in mre11 mutants, so the relationship is regulatory or pathway-choice rather than a catalytic step. Kept as non-core. Supporting Evidence: PMID:17321803 These results indicate that Mre11 functions in Rad51-independent BIR, and that Ku functions in Rad51-dependent BIR |
| GO:0000729 DNA double-strand break processing | IMP PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block... | ACCEPT | Summary: DNA double-strand break processing. Correct for S. cerevisiae Mre11, but the cited paper is a S. pombe study. Reason: Mre11 nicks the 5' strand and resects 3'->5' toward the break (PMID:22002605). Sae2 activates its dsDNA endonuclease on the 5' strand at blocked ends (PMID:25231868). This is the defining catalytic process of Mre11. The cited reference PMID:23080121 analyses S. pombe Rad32 mutants; see source_defects. Supporting Evidence: PMID:22002605 Mre11 nicks the strand to be resected up to 300 nucleotides from the 5'-terminus of the DSB PMID:25231868 The endonuclease preferentially cleaves the 5'-terminated dsDNA strand, which explains the polarity paradox PMID:23080121 Mre11 is also crucial in S. cerevisiae, although the effects of ablating its nuclease activities are weaker |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000044 | ACCEPT | Summary: Chromosome, telomeric region. Reason: ChIP shows MRX recruited to S. cerevisiae telomeres in late S phase (PMID:15721260), which directly supports this mapping. Supporting Evidence: PMID:15721260 MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase |
| GO:0003691 double-stranded telomeric DNA binding | IDA PMID:17698079 The characterization of Saccharomyces cerevisiae Mre11/Rad50... | KEEP AS NON CORE | Summary: Double-stranded telomeric DNA binding in vitro. Reason: MRX and its subunits bind telomeric dsDNA, but much less well than G4 DNA (PMID:17698079). This is an in vitro binding property of a DNA-end-processing nuclease, not a telomere-specific recognition function. Supporting Evidence: PMID:17698079 display an overwhelming preference for G-quadruplex DNA than for telomeric single-stranded or double-stranded DNA |
| GO:0004017 AMP kinase activity | IDA PMID:17349953 Rad50 adenylate kinase activity regulates DNA tethering by M... | KEEP AS NON CORE | Summary: Contributes to AMP (adenylate) kinase activity of Mre11-Rad50 complexes. Reason: The adenylate kinase reaction is catalysed by the Rad50 ABC-ATPase head; a Rad50 signature-motif mutant reduces it (PMID:17349953). Mre11 has no adenylate kinase active site. It contributes only as the partner subunit of the MR complex, which is the weaker claim the contributes_to qualifier makes. Kept as non-core. Supporting Evidence: PMID:17349953 Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro PMID:17349953 Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis |
| GO:0004519 endonuclease activity | IDA PMID:9858579 The nuclease activity of Mre11 is required for meiosis but n... | MODIFY | Summary: Endonuclease activity. Correct but more general than the established activities. Reason: S. cerevisiae Mre11 is a DNA endonuclease with two characterised modes. The first is ssDNA endonuclease activity (PMID:9858579). The second is Sae2-stimulated dsDNA endonuclease activity on the 5'-terminated strand next to protein-blocked ends (PMID:25231868). The generic term is replaced by these two descendants, which this review already carries or proposes. Proposed replacements: single-stranded DNA endonuclease activity double-stranded DNA endonuclease activity Supporting Evidence: PMID:9858579 the purified Mre11 protein was found to have single-stranded endonuclease activity PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex |
| GO:0004519 endonuclease activity | IEA GO_REF:0000002 | MODIFY | Summary: Endonuclease activity. Correct but more general than the established activities. Reason: S. cerevisiae Mre11 is a DNA endonuclease with two characterised modes. The first is ssDNA endonuclease activity (PMID:9858579). The second is Sae2-stimulated dsDNA endonuclease activity on the 5'-terminated strand next to protein-blocked ends (PMID:25231868). The generic term is replaced by these two descendants, which this review already carries or proposes. Proposed replacements: single-stranded DNA endonuclease activity double-stranded DNA endonuclease activity Supporting Evidence: PMID:9858579 the purified Mre11 protein was found to have single-stranded endonuclease activity PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex |
| GO:0004520 DNA endonuclease activity | IDA PMID:16116037 Saccharomyces cerevisiae Mre11 is a high-affinity G4 DNA-bin... | MODIFY | Summary: DNA endonuclease activity. Correct but less specific than the established ss- and dsDNA endonuclease activities. Reason: Ghosal & Muniyappa showed Mn2+-dependent endonucleolytic cleavage of G-rich single-stranded and G4 DNA by ScMre11 (PMID:16116037). Together with the ssDNA endonuclease (PMID:9858579) and Sae2-stimulated dsDNA endonuclease (PMID:25231868) data, this supports the two more specific descendant terms. Proposed replacements: single-stranded DNA endonuclease activity double-stranded DNA endonuclease activity Supporting Evidence: PMID:16116037 binding of ScMre11p to G4 DNA and G-rich single-stranded DNA was accompanied by the endonucleolytic cleavage at sites flanking the array of G residues and G-quartets in Mn2+-dependent manner PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex |
| GO:0004520 DNA endonuclease activity | IEA GO_REF:0000002 | MODIFY | Summary: DNA endonuclease activity. Correct but less specific than the established ss- and dsDNA endonuclease activities. Reason: Ghosal & Muniyappa showed Mn2+-dependent endonucleolytic cleavage of G-rich single-stranded and G4 DNA by ScMre11 (PMID:16116037). Together with the ssDNA endonuclease (PMID:9858579) and Sae2-stimulated dsDNA endonuclease (PMID:25231868) data, this supports the two more specific descendant terms. Proposed replacements: single-stranded DNA endonuclease activity double-stranded DNA endonuclease activity Supporting Evidence: PMID:16116037 binding of ScMre11p to G4 DNA and G-rich single-stranded DNA was accompanied by the endonucleolytic cleavage at sites flanking the array of G residues and G-quartets in Mn2+-dependent manner PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex |
| GO:0004520 DNA endonuclease activity | IMP PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block... | MODIFY | Summary: DNA endonuclease activity. The term is right for S. cerevisiae Mre11, but the cited paper is a S. pombe study. Reason: The endonuclease activity of S. cerevisiae Mre11 is well established (PMID:9858579, PMID:25231868), so the claim stands and is refined to the same specific terms as the other rows for this term. However, PMID:23080121 assays S. pombe Rad32 ATLD mutants and human MRE11 protein, not S. cerevisiae Mre11; see source_defects. Proposed replacements: single-stranded DNA endonuclease activity double-stranded DNA endonuclease activity Supporting Evidence: PMID:25231868 we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex PMID:23080121 Mre11 is also crucial in S. cerevisiae, although the effects of ablating its nuclease activities are weaker |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:14992724 Antiviral protein Ski8 is a direct partner of Spo11 in meiot... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:14992724 Antiviral protein Ski8 is a direct partner of Spo11 in meiot... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:20811460 Mechanism of the ATP-dependent DNA end-resection machinery f... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:20811460 Mechanism of the ATP-dependent DNA end-resection machinery f... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:21892167 The Rad50 coiled-coil domain is indispensable for Mre11 comp... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:21892167 The Rad50 coiled-coil domain is indispensable for Mre11 comp... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:23267104 Proteome-wide protein interaction measurements of bacterial ... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. The cited paper (a bacterial protein-interaction study) does not mention Mre11 or Xrs2, so the IntAct reference itself looks mis-keyed. |
| GO:0005515 protein binding | IPI PMID:25107472 DNA end recognition by the Mre11 nuclease dimer: insights in... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:25107472 DNA end recognition by the Mre11 nuclease dimer: insights in... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:25231868 Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:25231868 Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:25231868 Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50... | REMOVE | Summary: Generic protein binding with Sae2 (UniProtKB:P46946). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Sae2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:26901759 Tel1 and Rif2 Regulate MRX Functions in End-Tethering and Re... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:26901759 Tel1 and Rif2 Regulate MRX Functions in End-Tethering and Re... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:28134932 Eukaryotic Rad50 functions as a rod-shaped dimer. | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:28134932 Eukaryotic Rad50 functions as a rod-shaped dimer. | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | REMOVE | Summary: Generic protein binding with Rad50 (UniProtKB:P12753). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Rad50 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005515 protein binding | IPI PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | REMOVE | Summary: Generic protein binding with Xrs2 (UniProtKB:P33301). Reason: Generic protein binding is uninformative. Removing it does not dispute the interaction: the physical association with Xrs2 is real and is captured by part_of Mre11 complex (GO:0030870) and the molecular adaptor activity rows. |
| GO:0005634 nucleus | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: Nuclear localization. Reason: Mre11 acts on nuclear DNA. Its nuclear import depends on Xrs2, and an Mre11-NLS fusion bypasses several Xrs2 functions (PMID:15548595, PMID:27746018). Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage PMID:27746018 Xrs2/Nbs1 is essential for nuclear translocation of Mre11 |
| GO:0005634 nucleus | IDA PMID:15548595 Xrs2p regulates Mre11p translocation to the nucleus and play... | ACCEPT | Summary: Nuclear localization. Reason: Mre11 acts on nuclear DNA. Its nuclear import depends on Xrs2, and an Mre11-NLS fusion bypasses several Xrs2 functions (PMID:15548595, PMID:27746018). Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage PMID:27746018 Xrs2/Nbs1 is essential for nuclear translocation of Mre11 |
| GO:0005634 nucleus | IDA PMID:27746018 Xrs2 Dependent and Independent Functions of the Mre11-Rad50 ... | ACCEPT | Summary: Nuclear localization. Reason: Mre11 acts on nuclear DNA. Its nuclear import depends on Xrs2, and an Mre11-NLS fusion bypasses several Xrs2 functions (PMID:15548595, PMID:27746018). Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage PMID:27746018 Xrs2/Nbs1 is essential for nuclear translocation of Mre11 |
| GO:0005634 nucleus | IDA PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | ACCEPT | Summary: Nuclear localization. Reason: Mre11 acts on nuclear DNA. Its nuclear import depends on Xrs2, and an Mre11-NLS fusion bypasses several Xrs2 functions (PMID:15548595, PMID:27746018). Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage PMID:27746018 Xrs2/Nbs1 is essential for nuclear translocation of Mre11 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization. Reason: Mre11 acts on nuclear DNA. Its nuclear import depends on Xrs2, and an Mre11-NLS fusion bypasses several Xrs2 functions (PMID:15548595, PMID:27746018). Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage PMID:27746018 Xrs2/Nbs1 is essential for nuclear translocation of Mre11 |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-981784 | ACCEPT | Summary: Nucleoplasm, from the Reactome Spo11-removal reaction. Reason: Consistent with nuclear localization and action on chromosomal DNA ends (PMID:15548595). It is a slightly more specific term than nucleus. Supporting Evidence: PMID:15548595 No more function of Xrs2p than translocation of Mre11p from the cytoplasm to the nucleus is necessary for response to DNA damage Reactome:R-SCE-981784 SPO11 is removed from the DNA by cleavage of single strands 3' to the attached SPO11 |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Chromosome localization. Reason: MRX is recruited to chromosomal DSBs and telomeres in S. cerevisiae (PMID:15721260, PMID:35501303). The UniProt similarity statement, transferred from human MRE11, agrees with this direct yeast evidence. Supporting Evidence: PMID:15721260 MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase PMID:35501303 We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo |
| GO:0005694 chromosome | ISS GO_REF:0000024 | ACCEPT | Summary: Chromosome localization. Reason: MRX is recruited to chromosomal DSBs and telomeres in S. cerevisiae (PMID:15721260, PMID:35501303). The UniProt similarity statement, transferred from human MRE11, agrees with this direct yeast evidence. Supporting Evidence: PMID:15721260 MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase PMID:35501303 We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | KEEP AS NON CORE | Summary: Mitochondrion, from mitochondrial proteome surveys. Reason: High-throughput mitochondrial proteomics detected Mre11. This is supported functionally by the contribution of MRX to repair of induced mitochondrial DSBs (PMID:22214610). It is a minor pool relative to the nuclear function. Supporting Evidence: PMID:22214610 loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: Mitochondrion, from mitochondrial proteome surveys. Reason: High-throughput mitochondrial proteomics detected Mre11. This is supported functionally by the contribution of MRX to repair of induced mitochondrial DSBs (PMID:22214610). It is a minor pool relative to the nuclear function. Supporting Evidence: PMID:22214610 loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs |
| GO:0006281 DNA repair | IMP PMID:7789757 Interaction of Mre11 and Rad50: two proteins required for DN... | MODIFY | Summary: DNA repair. Correct but general. Reason: The repair defect of mre11 mutants (PMID:7789757) is a defect in DSB repair. Mre11 repairs MMS-induced DSBs by nuclease-dependent and nuclease-independent reactions (PMID:9845372). The more specific term double-strand break repair (GO:0006302), which the gene already carries, is preferred. Proposed replacements: double-strand break repair Supporting Evidence: PMID:7789757 A temperature-sensitive mre11-1 mutation of Saccharomyces cerevisiae causes defects in meiotic recombination and DNA repair during vegetative growth at a restrictive temperature PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing |
| GO:0006284 base-excision repair | IMP PMID:20040573 A novel function for the Mre11-Rad50-Xrs2 complex in base ex... | KEEP AS NON CORE | Summary: Base-excision repair. Reason: Steininger et al. report a BER deficiency in MRX mutants, acting downstream of the Ntg1/Ntg2 AP lyases. Most analyses used xrs2, but the authors state that all MRX subunits are similarly important (PMID:20040573). Base recognition and incision are unaffected, and the complex appears to support efficient gap filling. The mechanism is undefined, so this is non-core. Supporting Evidence: PMID:20040573 all components of the MRX complex are similarly important for the new function in BER PMID:20040573 Analysis of individual steps in BER showed that base recognition and strand incision are not affected by the MRX complex |
| GO:0006302 double-strand break repair | IEA GO_REF:0000002 | ACCEPT | Summary: Double-strand break repair. Reason: Mre11 nuclease activities are required for efficient DSB repair and confer resistance to DNA damage (PMID:22002605). MRX also supports NHEJ (PMID:12399380). The term spans both pathways, which suits a protein that acts in HR and NHEJ. Supporting Evidence: PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair |
| GO:0006302 double-strand break repair | IMP PMID:22002605 Bidirectional resection of DNA double-strand breaks by Mre11... | ACCEPT | Summary: Double-strand break repair. Reason: Mre11 nuclease activities are required for efficient DSB repair and confer resistance to DNA damage (PMID:22002605). MRX also supports NHEJ (PMID:12399380). The term spans both pathways, which suits a protein that acts in HR and NHEJ. Supporting Evidence: PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair PMID:22002605 Mre11 exonuclease activity also confers resistance to DNA damage in cycling cells |
| GO:0006302 double-strand break repair | NAS PMID:15716496 Isolation and characterization of novel xrs2 mutations in Sa... | ACCEPT | Summary: Double-strand break repair. Reason: Mre11 nuclease activities are required for efficient DSB repair and confer resistance to DNA damage (PMID:22002605). MRX also supports NHEJ (PMID:12399380). The term spans both pathways, which suits a protein that acts in HR and NHEJ. Supporting Evidence: PMID:15716496 While the Mre11-binding domain is essential for Xrs2 function |
| GO:0006303 double-strand break repair via nonhomologous end joining | IBA GO_REF:0000033 | ACCEPT | Summary: Nonhomologous end joining. Reason: MRE11 is one of the seven genes whose deletion causes frank loss of NHEJ in a genome-wide screen (PMID:12399380). It is also required for Ku-dependent DSB repair (PMID:9501103). Nuclease-dead alleles are NHEJ-proficient (PMID:9858579), so the contribution is structural, through MRX end bridging and Xrs2-mediated recruitment (PMID:27746018). Supporting Evidence: PMID:12399380 Seven mutants showed a decreased NHEJ/SSA ratio due to frank loss of NHEJ, which corresponded to all known structural/catalytic NHEJ components (yku70, yku80, dnl4, lif1, rad50, mre11, and xrs2) PMID:9501103 RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance PMID:9858579 Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant |
| GO:0006303 double-strand break repair via nonhomologous end joining | IMP PMID:12399380 A genomics-based screen for yeast mutants with an altered re... | ACCEPT | Summary: Nonhomologous end joining. Reason: MRE11 is one of the seven genes whose deletion causes frank loss of NHEJ in a genome-wide screen (PMID:12399380). It is also required for Ku-dependent DSB repair (PMID:9501103). Nuclease-dead alleles are NHEJ-proficient (PMID:9858579), so the contribution is structural, through MRX end bridging and Xrs2-mediated recruitment (PMID:27746018). Supporting Evidence: PMID:12399380 Seven mutants showed a decreased NHEJ/SSA ratio due to frank loss of NHEJ, which corresponded to all known structural/catalytic NHEJ components (yku70, yku80, dnl4, lif1, rad50, mre11, and xrs2) PMID:9858579 Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant |
| GO:0006303 double-strand break repair via nonhomologous end joining | IMP PMID:9501103 Components of the Ku-dependent non-homologous end-joining pa... | ACCEPT | Summary: Nonhomologous end joining. Reason: MRE11 is one of the seven genes whose deletion causes frank loss of NHEJ in a genome-wide screen (PMID:12399380). It is also required for Ku-dependent DSB repair (PMID:9501103). Nuclease-dead alleles are NHEJ-proficient (PMID:9858579), so the contribution is structural, through MRX end bridging and Xrs2-mediated recruitment (PMID:27746018). Supporting Evidence: PMID:9501103 RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance PMID:9858579 Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:17396017 Mre11 mediates gene regulation in yeast spore development. | MARK AS OVER ANNOTATED | Summary: Regulation of transcription by RNA polymerase II, inferred from impaired activation of about 90 meiotic genes in mre11 null cells. Reason: The single study measured an expression phenotype of mre11 deletion during meiosis (PMID:17396017). It does not show Mre11 acting at promoters, binding regulatory DNA, or interacting with the transcription machinery. The authors favour a C-terminus-dependent role, but the mechanism is unknown and could be indirect. Without evidence that Mre11 does part of the work of regulating transcription, the term over-reaches. Supporting Evidence: PMID:17396017 the activation of about 90 meiotic genes were severely and specifically impaired in early meiosis PMID:17396017 The transcriptional deficiency was not observed in other DSB mutants such as rad50Delta, xrs2Delta, spo11Delta, and spo11Y135F |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitotic G2 DNA damage checkpoint signaling (IBA, PTN000015644; donors are fly and mouse). Reason: MRX promotes DNA damage signaling through Tel1 (PMID:27746018, PMID:35501303), so a checkpoint role is consistent with the yeast data. No S. cerevisiae experiment cited here tests G2 checkpoint signaling specifically, and the IBA has no yeast donor. Accepted as an inherited family function, but non-core. Supporting Evidence: PMID:27746018 MRE11-NLS was unable to rescue the xrs2Ξ defects in Tel1/ATM kinase signaling and non-homologous end joining PMID:35501303 We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo |
| GO:0007131 reciprocal meiotic recombination | IMP PMID:8417989 Identification of new genes required for meiotic recombinati... | ACCEPT | Summary: Reciprocal meiotic recombination. Reason: MRE11 was identified in a screen for meiotic recombination mutants. mre11 spores are rescued by spo13, which places the block early in meiotic recombination (PMID:8417989). Mre11 is needed both for Spo11 DSB formation (PMID:7789757) and for nucleolytic processing of the breaks (PMID:9858579). Supporting Evidence: PMID:8417989 The mre2 and mre11 mutants produce viable spores in a spo13 background, in which meiosis I is bypassed, suggesting that these mutants are blocked at an early step in meiotic recombination PMID:9858579 Diploids homozygous for the mre11-H125N mutation failed to sporulate and accumulated unresected double-strand breaks (DSB) during meiosis |
| GO:0008296 3'-5'-DNA exonuclease activity | IEA GO_REF:0000002 | ACCEPT | Summary: 3'-5'-DNA exonuclease activity of the Mre11 nuclease domain. Reason: Purified S. cerevisiae Mre11 releases mononucleotides 3'->5', with a preference for duplex ends (PMID:11454871). In vivo, the Mre11 exonuclease resects Spo11-linked 5' termini back toward the DSB end after the endonucleolytic nick (PMID:22002605). This is a core catalytic activity. Supporting Evidence: PMID:11454871 Mre11 has a 3' to 5' exonuclease activity that results in the release of mononucleotides PMID:22002605 Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair |
| GO:0008296 3'-5'-DNA exonuclease activity | IMP PMID:22002605 Bidirectional resection of DNA double-strand breaks by Mre11... | ACCEPT | Summary: 3'-5'-DNA exonuclease activity of the Mre11 nuclease domain. Reason: Purified S. cerevisiae Mre11 releases mononucleotides 3'->5', with a preference for duplex ends (PMID:11454871). In vivo, the Mre11 exonuclease resects Spo11-linked 5' termini back toward the DSB end after the endonucleolytic nick (PMID:22002605). This is a core catalytic activity. Supporting Evidence: PMID:11454871 Mre11 has a 3' to 5' exonuclease activity that results in the release of mononucleotides PMID:22002605 Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair |
| GO:0008296 3'-5'-DNA exonuclease activity | TAS Reactome:R-SCE-981784 | ACCEPT | Summary: 3'-5'-DNA exonuclease activity of the Mre11 nuclease domain. Reason: Purified S. cerevisiae Mre11 releases mononucleotides 3'->5', with a preference for duplex ends (PMID:11454871). In vivo, the Mre11 exonuclease resects Spo11-linked 5' termini back toward the DSB end after the endonucleolytic nick (PMID:22002605). This is a core catalytic activity. Supporting Evidence: PMID:11454871 Mre11 has a 3' to 5' exonuclease activity that results in the release of mononucleotides PMID:22002605 Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo PMID:22002605 the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair |
| GO:0008408 3'-5' exonuclease activity | IDA PMID:11454871 DNA structure-specific nuclease activities in the Saccharomy... | MODIFY | Summary: 3'-5' exonuclease activity, measured on DNA substrates. Reason: The assay used DNA oligonucleotide substrates (PMID:11454871), so the DNA-specific child term GO:0008296 3'-5'-DNA exonuclease activity is the accurate term. The gene already carries it from other evidence. Proposed replacements: 3'-5'-DNA exonuclease activity Supporting Evidence: PMID:11454871 Mre11 has a 3' to 5' exonuclease activity that results in the release of mononucleotides |
| GO:0010780 meiotic DNA double-strand break formation involved in reciprocal meiotic recombination | IMP PMID:7625279 Functions of the yeast meiotic recombination genes, MRE11 an... | ACCEPT | Summary: Meiotic DSB formation involved in reciprocal meiotic recombination. Reason: Meiosis-specific DSBs at hotspots are absent in mre11 mutants (PMID:7625279, PMID:7789757). The role is nuclease-independent and maps to the Mre11 C-terminal region, which binds meiotic proteins (PMID:9845372). It is specific to S. cerevisiae and should not be transferred to other species without evidence. Supporting Evidence: PMID:7625279 neither meiosis specific DSBs at recombination hot-spots nor formation of synaptonemal complex occur in either mutant PMID:7789757 In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished PMID:9845372 The C-terminal region of Mre11 is required only for DSB formation and binds to some meiotic proteins |
| GO:0010791 DNA double-strand break processing involved in repair via synthesis-dependent strand annealing | IMP PMID:23254329 Competing roles of DNA end resection and non-homologous end ... | ACCEPT | Summary: DSB processing involved in repair via SDSA (sister-chromatid recombination). Reason: MRX, and in particular the Mre11 nuclease, together with Sae2, is required for SCR-mediated repair of replication-born DSBs (PMID:23254329). This is the nuclease end-processing function in a specific HR context. Supporting Evidence: PMID:23254329 We provide evidence that MRX, particularly its Mre11 nuclease activity, and Sae2 are required for SCR-mediated repair of DSBs |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Hydrolase activity from the calcineurin-like phosphoesterase InterPro signature. Reason: True, but entailed by the specific nuclease activities accepted in this review (ssDNA endonuclease, dsDNA endonuclease, 3'-5'-DNA exonuclease). Supporting Evidence: file:yeast/MRE11/MRE11-uniprot.txt Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity |
| GO:0030145 manganese ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Manganese ion binding as the nuclease cofactor. Reason: Mre11 nuclease activities are Mn2+-dependent in vitro (PMID:16116037). The UniProt cofactor annotation transfers Mn2+ coordination from the Chaetomium SF1 structure (G0RYR3). Cofactor binding is accurate but secondary to the catalytic function. Supporting Evidence: PMID:16116037 binding of ScMre11p to G4 DNA and G-rich single-stranded DNA was accompanied by the endonucleolytic cleavage at sites flanking the array of G residues and G-quartets in Mn2+-dependent manner file:yeast/MRE11/MRE11-uniprot.txt Name=Mn(2+); Xref=ChEBI:CHEBI:29035 |
| GO:0030437 ascospore formation | IMP PMID:17396017 Mre11 mediates gene regulation in yeast spore development. | MARK AS OVER ANNOTATED | Summary: Ascospore formation, from fragile spore walls and reduced expression of spore-wall genes in mre11 null cells. Reason: Spore defects in mre11 mutants are downstream of failed meiotic recombination and possibly altered meiotic gene expression (PMID:17396017). Mre11 does no part of the work of building the spore. These are downstream organismal phenotypes, not process participation. Supporting Evidence: PMID:17396017 the activation of about 90 meiotic genes were severely and specifically impaired in early meiosis |
| GO:0030437 ascospore formation | IMP PMID:7625279 Functions of the yeast meiotic recombination genes, MRE11 an... | MARK AS OVER ANNOTATED | Summary: Ascospore formation, from the inviable-spore phenotype. Reason: The spore inviability of mre11 is bypassed by spo13, so it results from failed meiotic DSB formation and processing, not from a role in spore morphogenesis (PMID:7625279, PMID:8417989). The phenotype is downstream. Supporting Evidence: PMID:7625279 The mre2 and mre11 deletion mutants are proficient in mitotic recombination, but are defective in meiotic recombination and in formation of viable spores PMID:8417989 The mre2 and mre11 mutants produce viable spores in a spo13 background, in which meiosis I is bypassed, suggesting that these mutants are blocked at an early step in meiotic recombination |
| GO:0030870 Mre11 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Part of the Mre11 complex (MRX: Mre11-Rad50-Xrs2). Reason: Mre11 forms a stable complex with Rad50 and Xrs2 and is its binding core (PMID:9845372). MR and MRX complexes purified from S. cerevisiae are active in cleaving protein-blocked ends (PMID:27746018). Membership is conserved across PTHR10139. Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:27746018 the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends |
| GO:0030870 Mre11 complex | IDA PMID:27746018 Xrs2 Dependent and Independent Functions of the Mre11-Rad50 ... | ACCEPT | Summary: Part of the Mre11 complex (MRX: Mre11-Rad50-Xrs2). Reason: Mre11 forms a stable complex with Rad50 and Xrs2 and is its binding core (PMID:9845372). MR and MRX complexes purified from S. cerevisiae are active in cleaving protein-blocked ends (PMID:27746018). Membership is conserved across PTHR10139. Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:27746018 the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends |
| GO:0030870 Mre11 complex | IEA GO_REF:0000120 | ACCEPT | Summary: Part of the Mre11 complex (MRX: Mre11-Rad50-Xrs2). Reason: Mre11 forms a stable complex with Rad50 and Xrs2 and is its binding core (PMID:9845372). MR and MRX complexes purified from S. cerevisiae are active in cleaving protein-blocked ends (PMID:27746018). Membership is conserved across PTHR10139. Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:27746018 the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends |
| GO:0030870 Mre11 complex | IPI PMID:27746018 Xrs2 Dependent and Independent Functions of the Mre11-Rad50 ... | ACCEPT | Summary: Part of the Mre11 complex (MRX: Mre11-Rad50-Xrs2). Reason: Mre11 forms a stable complex with Rad50 and Xrs2 and is its binding core (PMID:9845372). MR and MRX complexes purified from S. cerevisiae are active in cleaving protein-blocked ends (PMID:27746018). Membership is conserved across PTHR10139. Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:27746018 the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends |
| GO:0030870 Mre11 complex | IPI PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | ACCEPT | Summary: Part of the Mre11 complex (MRX: Mre11-Rad50-Xrs2). Reason: Mre11 forms a stable complex with Rad50 and Xrs2 and is its binding core (PMID:9845372). MR and MRX complexes purified from S. cerevisiae are active in cleaving protein-blocked ends (PMID:27746018). Membership is conserved across PTHR10139. Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:27746018 the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends |
| GO:0031573 mitotic intra-S DNA damage checkpoint signaling | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitotic intra-S DNA damage checkpoint signaling (IBA from PTN000015646; donors are mouse and S. pombe). Reason: This IBA comes from PTN000015646, not the root node. S. cerevisiae inherits it as a member of the descendant clade. MRX-dependent Tel1 signaling in yeast (PMID:27746018) is consistent with it, but no yeast intra-S checkpoint assay is cited. Non-core. Supporting Evidence: PMID:27746018 MRE11-NLS was unable to rescue the xrs2Ξ defects in Tel1/ATM kinase signaling and non-homologous end joining |
| GO:0035753 maintenance of DNA trinucleotide repeats | IMP PMID:27173583 The Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex promot... | MARK AS OVER ANNOTATED | Summary: Maintenance of DNA trinucleotide repeats. Reason: GO:0035753 is defined as processes sustaining the fidelity and copy number of trinucleotide repeats. Ye et al. show the opposite: MRX promotes expansions of short TNRs, and MRX loss suppresses them. The Mre11 nuclease is dispensable for this (PMID:27173583). Mre11 therefore destabilizes TNRs, so the term misstates the direction of the effect. GO lacks a term for TNR expansion (see suggested_questions). Supporting Evidence: PMID:27173583 Mutations that eliminate MRX subunits led to significant suppression of expansions whereas mutations that inactivate Rad51 had only a minor effect PMID:27173583 The nuclease function of Mre11 was dispensable for expansions |
| GO:0035861 site of double-strand break | IBA GO_REF:0000033 | ACCEPT | Summary: Active at sites of double-strand breaks (IBA, PTN000015644). Reason: Mre11-Rad50 oligomers form foci at DSBs, and MRX is the first complex to engage break ends in S. cerevisiae (PMID:35501303, PMID:14522986). The family-root placement is appropriate. Supporting Evidence: PMID:35501303 We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo PMID:14522986 Importantly, we demonstrate that Xrs2 is critical for targeting of Rad50 and Mre11 to DNA ends |
| GO:0042138 meiotic DNA double-strand break formation | IBA GO_REF:0000033 | ACCEPT | Summary: Meiotic DNA double-strand break formation. Reason: S. cerevisiae Mre11 is required for Spo11-dependent meiotic DSB formation (PMID:7789757, PMID:7625279), through its C-terminal region (PMID:9845372). The yeast gene is an experimental donor to this IBA. Note for transfer: the requirement is nuclease-independent and mechanistically tied to S. cerevisiae meiotic DSB proteins. Supporting Evidence: PMID:7789757 In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished PMID:9845372 The C-terminal region of Mre11 is required only for DSB formation and binds to some meiotic proteins |
| GO:0042138 meiotic DNA double-strand break formation | IMP PMID:22002605 Bidirectional resection of DNA double-strand breaks by Mre11... | ACCEPT | Summary: Meiotic DNA double-strand break formation. Reason: S. cerevisiae Mre11 is required for Spo11-dependent meiotic DSB formation (PMID:7789757, PMID:7625279), through its C-terminal region (PMID:9845372). The yeast gene is an experimental donor to this IBA. Note for transfer: the requirement is nuclease-independent and mechanistically tied to S. cerevisiae meiotic DSB proteins. Supporting Evidence: PMID:7789757 In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished |
| GO:0042138 meiotic DNA double-strand break formation | IMP PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block... | ACCEPT | Summary: Meiotic DSB formation. True for S. cerevisiae Mre11, but not shown by the cited S. pombe paper. Reason: The claim is supported in S. cerevisiae (PMID:7789757, PMID:9845372), so the term is kept, consistent with the other rows for it. PMID:23080121 studies S. pombe Rad32 and measures spore viability and DSB repair in meiosis, not meiotic DSB formation, so the reference supports neither the organism nor the term; see source_defects. Supporting Evidence: PMID:7789757 In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished PMID:23080121 Mre11 is also crucial in S. cerevisiae, although the effects of ablating its nuclease activities are weaker |
| GO:0042138 meiotic DNA double-strand break formation | NAS PMID:15716496 Isolation and characterization of novel xrs2 mutations in Sa... | ACCEPT | Summary: Meiotic DNA double-strand break formation. Reason: S. cerevisiae Mre11 is required for Spo11-dependent meiotic DSB formation (PMID:7789757, PMID:7625279), through its C-terminal region (PMID:9845372). The yeast gene is an experimental donor to this IBA. Note for transfer: the requirement is nuclease-independent and mechanistically tied to S. cerevisiae meiotic DSB proteins. Supporting Evidence: PMID:7789757 In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished |
| GO:0042162 telomeric repeat DNA binding | IDA PMID:15721260 Late S phase-specific recruitment of Mre11 complex triggers ... | KEEP AS NON CORE | Summary: Telomeric repeat DNA binding. Reason: PMID:16116037 shows in vitro binding of G-rich telomeric DNA. PMID:15721260 shows by ChIP that MRX is recruited to telomeres in late S phase, which is association with telomeric chromatin rather than sequence-specific binding. MRX acts at telomeres by recruiting Tel1 and Mec1, and this does not need the Mre11 nuclease (PMID:9858579). Kept as non-core. Supporting Evidence: PMID:15721260 MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase |
| GO:0042162 telomeric repeat DNA binding | IDA PMID:16116037 Saccharomyces cerevisiae Mre11 is a high-affinity G4 DNA-bin... | KEEP AS NON CORE | Summary: Telomeric repeat DNA binding. Reason: PMID:16116037 shows in vitro binding of G-rich telomeric DNA. PMID:15721260 shows by ChIP that MRX is recruited to telomeres in late S phase, which is association with telomeric chromatin rather than sequence-specific binding. MRX acts at telomeres by recruiting Tel1 and Mec1, and this does not need the Mre11 nuclease (PMID:9858579). Kept as non-core. Supporting Evidence: PMID:16116037 S.cerevisiae Mre11 protein (ScMre11p) possesses substantially higher binding affinity for G4 DNA, over single- or double-stranded DNA |
| GO:0043047 single-stranded telomeric DNA binding | IDA PMID:17698079 The characterization of Saccharomyces cerevisiae Mre11/Rad50... | KEEP AS NON CORE | Summary: Single-stranded telomeric DNA binding in vitro. Reason: Binding of G-rich telomeric ssDNA is documented in vitro (PMID:17698079, PMID:16116037). It is plausible in the context of MRX recruitment to telomeres in late S phase, but peripheral. Supporting Evidence: PMID:17698079 display an overwhelming preference for G-quadruplex DNA than for telomeric single-stranded or double-stranded DNA PMID:16116037 S.cerevisiae Mre11 protein (ScMre11p) possesses substantially higher binding affinity for G4 DNA, over single- or double-stranded DNA |
| GO:0051321 meiotic cell cycle | IMP PMID:17396017 Mre11 mediates gene regulation in yeast spore development. | MODIFY | Summary: Meiotic cell cycle. Correct but general. Reason: The meiotic requirement for Mre11 lies in meiotic recombination: Spo11-DSB formation and processing (PMID:7789757, PMID:9858579). The specific term reciprocal meiotic recombination (GO:0007131), already on the gene, is preferred. Proposed replacements: reciprocal meiotic recombination Supporting Evidence: PMID:17396017 the activation of about 90 meiotic genes were severely and specifically impaired in early meiosis PMID:8417989 The mre2 and mre11 mutants produce viable spores in a spo13 background, in which meiosis I is bypassed, suggesting that these mutants are blocked at an early step in meiotic recombination |
| GO:0051880 G-quadruplex DNA binding | IDA PMID:17698079 The characterization of Saccharomyces cerevisiae Mre11/Rad50... | KEEP AS NON CORE | Summary: G-quadruplex DNA binding. Reason: Two independent studies from the same group report high-affinity G4 DNA binding by ScMre11 (PMID:16116037, PMID:17698079). The in vivo significance at telomeres remains to be shown, so this is non-core. Supporting Evidence: PMID:16116037 S.cerevisiae Mre11 protein (ScMre11p) possesses substantially higher binding affinity for G4 DNA, over single- or double-stranded DNA PMID:17698079 display an overwhelming preference for G-quadruplex DNA than for telomeric single-stranded or double-stranded DNA |
| GO:0060090 molecular adaptor activity | IGI PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | ACCEPT | Summary: Molecular adaptor activity: Mre11 is the binding core that bridges Rad50 and Xrs2 in MRX. Reason: Usui et al. showed that Mre11 is the binding core of the MRX complex. It has two Rad50-binding regions, and its C-terminal region binds meiotic DSB proteins and is needed only for DSB formation (PMID:9845372). Xrs2 binds the complex through its Mre11-binding domain (PMID:15716496). This structural role explains the nuclease-independent functions of Mre11 in NHEJ, telomere maintenance and meiotic DSB formation (PMID:9858579). Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:9845372 It has two regions to bind to Rad50 PMID:9845372 The C-terminal region of Mre11 is required only for DSB formation and binds to some meiotic proteins PMID:15716496 While the Mre11-binding domain is essential for Xrs2 function |
| GO:0060090 molecular adaptor activity | IGI PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | ACCEPT | Summary: Molecular adaptor activity: Mre11 is the binding core that bridges Rad50 and Xrs2 in MRX. Reason: Usui et al. showed that Mre11 is the binding core of the MRX complex. It has two Rad50-binding regions, and its C-terminal region binds meiotic DSB proteins and is needed only for DSB formation (PMID:9845372). Xrs2 binds the complex through its Mre11-binding domain (PMID:15716496). This structural role explains the nuclease-independent functions of Mre11 in NHEJ, telomere maintenance and meiotic DSB formation (PMID:9858579). Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:9845372 It has two regions to bind to Rad50 PMID:9845372 The C-terminal region of Mre11 is required only for DSB formation and binds to some meiotic proteins PMID:15716496 While the Mre11-binding domain is essential for Xrs2 function |
| GO:0060090 molecular adaptor activity | IMP PMID:9845372 Complex formation and functional versatility of Mre11 of bud... | ACCEPT | Summary: Molecular adaptor activity: Mre11 is the binding core that bridges Rad50 and Xrs2 in MRX. Reason: Usui et al. showed that Mre11 is the binding core of the MRX complex. It has two Rad50-binding regions, and its C-terminal region binds meiotic DSB proteins and is needed only for DSB formation (PMID:9845372). Xrs2 binds the complex through its Mre11-binding domain (PMID:15716496). This structural role explains the nuclease-independent functions of Mre11 in NHEJ, telomere maintenance and meiotic DSB formation (PMID:9858579). Supporting Evidence: PMID:9845372 Mre11 forms a complex with Rad50 and Xrs2, acting as the binding core, and participates in DSB processing PMID:9845372 It has two regions to bind to Rad50 PMID:9845372 The C-terminal region of Mre11 is required only for DSB formation and binds to some meiotic proteins PMID:15716496 While the Mre11-binding domain is essential for Xrs2 function |
| GO:0062176 R-loop processing | IDA PMID:31537797 MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression ... | UNDECIDED | Summary: R-loop processing. Reason: Chang et al. found MRN to be required to suppress R-loops at transcription-replication conflicts. The yeast experiments used rad50Ξ, and the authors state that mre11Ξ triple mutants were not made. The non-nucleolytic MRE11 function was shown in human cells (PMID:31537797). For S. cerevisiae Mre11 this is a complex-level inference, not a direct IDA, and 'R-loop processing' may overstate a suppression role. Left undecided pending yeast mre11-specific data. Supporting Evidence: PMID:31537797 MRE11 and RNH1 are linked genes on yeast chrXIII so triple mutants with mre11Ξ were not made |
| GO:0097552 mitochondrial double-strand break repair via homologous recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial DSB repair via homologous recombination. Reason: Loss of MRX alters mtDNA deletion rates and impairs repair of induced mtDSBs. MRX and Ku act partially redundantly in mitochondria, where HR is the predominant pathway (PMID:22214610). This is real but peripheral to the nuclear function. Supporting Evidence: PMID:22214610 loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs |
| GO:0097552 mitochondrial double-strand break repair via homologous recombination | IMP PMID:22214610 Mitochondrial genome maintenance: roles for nuclear nonhomol... | KEEP AS NON CORE | Summary: Mitochondrial DSB repair via homologous recombination. Reason: Loss of MRX alters mtDNA deletion rates and impairs repair of induced mtDSBs. MRX and Ku act partially redundantly in mitochondria, where HR is the predominant pathway (PMID:22214610). This is real but peripheral to the nuclear function. Supporting Evidence: PMID:22214610 loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs |
| GO:0000706 meiotic DNA double-strand break processing | IMP PMID:9858579 The nuclease activity of Mre11 is required for meiosis but n... | NEW | Summary: Meiotic DNA double-strand break processing: nucleolytic release of Spo11 and resection of meiotic DSB ends. Reason: Mre11 catalyses steps of this process. Nuclease-dead mre11-H125N diploids accumulate unresected meiotic DSBs (PMID:9858579). In vivo, Mre11 nicks Spo11-linked 5' strands and resects them 3'->5' (PMID:22002605), and the Reactome Spo11-removal reaction reflects the same chemistry. The participation test is passed because Mre11 is the nuclease that performs the cleavage. The term is not a parent or child of the GO:0042138 / GO:0010780 formation terms already carried. Supporting Evidence: PMID:9858579 Diploids homozygous for the mre11-H125N mutation failed to sporulate and accumulated unresected double-strand breaks (DSB) during meiosis PMID:22002605 Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo PMID:22002605 Mre11 nicks the strand to be resected up to 300 nucleotides from the 5'-terminus of the DSB |
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Download this section (compressed HTML)Q: GO has no term for trinucleotide repeat expansion or instability. MRX promotes TNR expansions (PMID:27173583), but the only available term, 'maintenance of DNA trinucleotide repeats', implies the opposite. Should a 'DNA trinucleotide repeat expansion' process term (or a negative-regulation sibling) be created?
Q: Is the meiotic-gene activation defect of mre11Ξ, which is not shared by rad50Ξ or xrs2Ξ (PMID:17396017), a direct transcriptional role of the Mre11 C-terminus or an indirect consequence of altered meiotic chromosome structure?
Q: Does Mre11 itself, rather than only Rad50/MRN, suppress R-loops at transcription-replication conflicts in S. cerevisiae, given that mre11Ξ triple mutants with rnh1Ξ rnh201Ξ could not be built (PMID:31537797)?
Experiment: Use separation-of-function alleles (nuclease-dead H125N vs. C-terminal truncation) in an rnh1Ξ rnh201Ξ background, built with a non-linked RNH1 marker or an auxin degron of Mre11. Measure DRIP-seq R-loop levels, to test whether yeast Mre11 suppresses R-loops and whether this needs the nuclease.
Experiment: Map promoter occupancy of Mre11 (ChIP-seq) during early meiosis at the ~90 Mre11-dependent spore-development genes, comparing wild type and mre11ΞC49, to test whether the transcriptional effect is direct.
Nuclease subunit of the MRX complex with Rad50p and Xrs2p; complex functions in repair of DNA double-strand breaks and in telomere stability; Mre11p associates with Ser/Thr-rich ORFs in premeiotic phase; nuclease activity required for MRX function; widely conserved; forms nuclear foci upon DNA replication stress
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