Mre11 (Rad32) is the DNA-binding nuclease subunit of the nuclear Mre11-Rad50-Nbs1 complex. It helps recognize and tether DNA double-strand breaks, coordinates DNA-end processing with Ctp1, and supports homologous recombination, selected nonhomologous end-joining reactions, telomere maintenance, and DNA damage signaling. Its conserved nuclease domain has endonucleolytic and 3′-to-5′ exonucleolytic activities. During meiosis it processes Rec12-linked DNA ends for repair and can initiate a separate palindrome-associated breakage pathway.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0000014 single-stranded DNA endonuclease activity
IBA GO_REF:0000033
ACCEPT
Summary: single-stranded DNA endonuclease activity is supported.
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
We show that the Rad50-Mre11-p95 complex possesses manganese-dependent single-stranded DNA endonuclease and 3' to 5' exonuclease activities.
GO:0000014 single-stranded DNA endonuclease activity
ISO PMID:9651580 The 3' to 5' exonuclease activity of Mre 11 facilitates repa...
ACCEPT
Summary: single-stranded DNA endonuclease activity is supported.
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
ISO PMID:18854158 Mre11 dimers coordinate DNA end bridging and nuclease proces...
ACCEPT
Summary: Y-form DNA binding is supported.
Reason: DNA-complex structures resolve how the conserved Mre11 dimer engages branched substrates and DNA ends. Fission yeast mutational analysis links this architecture to MRN assembly and break repair, supporting the curated orthology transfer rather than a claim of a target-only binding assay.
To define the roles of Mre11 in both DNA bridging and nucleolytic processing during initiation of DSB repair, we combined small-angle X-ray scattering (SAXS) and crystal structures of Pyrococcus furiosus Mre11 dimers bound to DNA with mutational analyses of fission yeast Mre11.
Reason: Rad32 associates with fission yeast telomeres by chromatin immunoprecipitation and functions with Tel1 in telomere maintenance. Telomeric residence and maintenance are established functions of the complex.
IGI PMID:12861005 Competition between the Rad50 complex and the Ku heterodimer...
ACCEPT
Summary: telomere maintenance is supported.
Reason: Rad32 associates with fission yeast telomeres by chromatin immunoprecipitation and functions with Tel1 in telomere maintenance. Telomeric residence and maintenance are established functions of the complex. The original PMID:12861005 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
These activities require Mre11-Rad50, which localizes to DSBs and bind Tel1 in the absence of Nbs1.
GO:0000724 double-strand break repair via homologous recombination
IBA GO_REF:0000033
ACCEPT
Summary: double-strand break repair via homologous recombination is supported.
Reason: Fission yeast rad32 mutants are defective in physical DSB repair and efficient homologous gene conversion. This is a central repair role of MRN, encompassing DNA-end coordination and nuclease-dependent removal of end-bound obstacles.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
GO:0000724 double-strand break repair via homologous recombination
IMP PMID:12628934 Pathway utilization in response to a site-specific DNA doubl...
ACCEPT
Summary: double-strand break repair via homologous recombination is supported.
Reason: Fission yeast rad32 mutants are defective in physical DSB repair and efficient homologous gene conversion. This is a central repair role of MRN, encompassing DNA-end coordination and nuclease-dependent removal of end-bound obstacles.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:19139281 Ctp1CtIP and Rad32Mre11 nuclease activity are required for R...
ACCEPT
Summary: DNA double-strand break processing is supported.
Reason: Mre11/Rad32 and Ctp1 process damaged DNA ends, including removal of covalent Rec12 complexes in meiosis and displacement of Ku/MRN to expose DNA for RPA and homologous recombination. The requirement for Mre11 protein must be distinguished from the requirement for its nuclease chemistry in particular resection assays.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:19752195 Meiotic DNA double-strand break repair requires two nuclease...
ACCEPT
Summary: DNA double-strand break processing is supported.
Reason: Mre11/Rad32 and Ctp1 process damaged DNA ends, including removal of covalent Rec12 complexes in meiosis and displacement of Ku/MRN to expose DNA for RPA and homologous recombination. The requirement for Mre11 protein must be distinguished from the requirement for its nuclease chemistry in particular resection assays.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:19911044 Ctp1 and the MRN-complex are required for endonucleolytic Re...
ACCEPT
Summary: DNA double-strand break processing is supported.
Reason: Mre11/Rad32 and Ctp1 process damaged DNA ends, including removal of covalent Rec12 complexes in meiosis and displacement of Ku/MRN to expose DNA for RPA and homologous recombination. The requirement for Mre11 protein must be distinguished from the requirement for its nuclease chemistry in particular resection assays.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:21931565 Release of Ku and MRN from DNA ends by Mre11 nuclease activi...
ACCEPT
Summary: DNA double-strand break processing is supported.
Reason: Mre11/Rad32 and Ctp1 process damaged DNA ends, including removal of covalent Rec12 complexes in meiosis and displacement of Ku/MRN to expose DNA for RPA and homologous recombination. The requirement for Mre11 protein must be distinguished from the requirement for its nuclease chemistry in particular resection assays.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block...
ACCEPT
Summary: DNA double-strand break processing is supported.
Reason: Mre11/Rad32 and Ctp1 process damaged DNA ends, including removal of covalent Rec12 complexes in meiosis and displacement of Ku/MRN to expose DNA for RPA and homologous recombination. The requirement for Mre11 protein must be distinguished from the requirement for its nuclease chemistry in particular resection assays.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
Summary: chromosome, telomeric region is supported.
Reason: Rad32 associates with fission yeast telomeres by chromatin immunoprecipitation and functions with Tel1 in telomere maintenance. Telomeric residence and maintenance are established functions of the complex.
IDA PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: nuclease activity is supported.
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
IPI PMID:12944481 Molecular characterization of the Schizosaccharomyces pombe ...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary. The original PMID:12944481 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:12944481 Molecular characterization of the Schizosaccharomyces pombe ...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary. The original PMID:12944481 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:12944482 The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is requir...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:18854158 Mre11 dimers coordinate DNA end bridging and nuclease proces...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
To define the roles of Mre11 in both DNA bridging and nucleolytic processing during initiation of DSB repair, we combined small-angle X-ray scattering (SAXS) and crystal structures of Pyrococcus furiosus Mre11 dimers bound to DNA with mutational analyses of fission yeast Mre11.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:21441914 ABC ATPase signature helices in Rad50 link nucleotide state ...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary. The original PMID:21441914 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
IPI PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block...
KEEP AS NON CORE
Summary: protein binding is retained as an ancillary annotation.
Reason: Retain the reported physical interaction as supporting complex-assembly evidence. Generic protein binding does not specify the nuclease or RNA-binding function and is not a useful core molecular-function summary.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
EXP PMID:12944482 The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is requir...
ACCEPT
Summary: nucleus is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
NAS PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: nucleus is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
EXP PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block...
ACCEPT
Summary: chromosome is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
Reason: Fission yeast rad32 mutants are defective in physical DSB repair and efficient homologous gene conversion. This is a central repair role of MRN, encompassing DNA-end coordination and nuclease-dependent removal of end-bound obstacles.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
IMP PMID:7885834 Cloning and characterisation of the Schizosaccharomyces pomb...
ACCEPT
Summary: double-strand break repair is supported.
Reason: Fission yeast rad32 mutants are defective in physical DSB repair and efficient homologous gene conversion. This is a central repair role of MRN, encompassing DNA-end coordination and nuclease-dependent removal of end-bound obstacles.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
NAS PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: double-strand break repair is supported.
Reason: Fission yeast rad32 mutants are defective in physical DSB repair and efficient homologous gene conversion. This is a central repair role of MRN, encompassing DNA-end coordination and nuclease-dependent removal of end-bound obstacles.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
GO:0006303 double-strand break repair via nonhomologous end joining
IBA GO_REF:0000033
ACCEPT
Summary: double-strand break repair via nonhomologous end joining is supported.
Reason: Fission yeast experiments support an MRN contribution to nonhomologous end joining, especially tethering dysfunctional telomeres or nonligatable hairpin-ended substrates. This does not imply its nuclease activity is required for every NHEJ reaction.
S. pombe NHEJ was reduced >1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction.
GO:0006303 double-strand break repair via nonhomologous end joining
IGI PMID:23188080 The fission yeast MRN complex tethers dysfunctional telomere...
ACCEPT
Summary: double-strand break repair via nonhomologous end joining is supported.
Reason: Fission yeast experiments support an MRN contribution to nonhomologous end joining, especially tethering dysfunctional telomeres or nonligatable hairpin-ended substrates. This does not imply its nuclease activity is required for every NHEJ reaction.
S. pombe NHEJ was reduced >1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction.
GO:0006303 double-strand break repair via nonhomologous end joining
IMP PMID:10373582 The role of Schizosaccharomyces pombe Rad32, the Mre11 homol...
ACCEPT
Summary: double-strand break repair via nonhomologous end joining is supported.
Reason: Fission yeast experiments support an MRN contribution to nonhomologous end joining, especially tethering dysfunctional telomeres or nonligatable hairpin-ended substrates. This does not imply its nuclease activity is required for every NHEJ reaction. The original PMID:10373582 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
S. pombe NHEJ was reduced >1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction.
GO:0006303 double-strand break repair via nonhomologous end joining
IMP PMID:23188080 The fission yeast MRN complex tethers dysfunctional telomere...
ACCEPT
Summary: double-strand break repair via nonhomologous end joining is supported.
Reason: Fission yeast experiments support an MRN contribution to nonhomologous end joining, especially tethering dysfunctional telomeres or nonligatable hairpin-ended substrates. This does not imply its nuclease activity is required for every NHEJ reaction.
S. pombe NHEJ was reduced >1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction.
GO:0006303 double-strand break repair via nonhomologous end joining
IMP PMID:28292918 Nonhomologous End-Joining with Minimal Sequence Loss Is Prom...
ACCEPT
Summary: double-strand break repair via nonhomologous end joining is supported.
Reason: Fission yeast experiments support an MRN contribution to nonhomologous end joining, especially tethering dysfunctional telomeres or nonligatable hairpin-ended substrates. This does not imply its nuclease activity is required for every NHEJ reaction.
S. pombe NHEJ was reduced >1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction.
GO:0007095 mitotic G2 DNA damage checkpoint signaling
IBA GO_REF:0000033
UNDECIDED
Summary: mitotic G2 DNA damage checkpoint signaling is not fully resolved.
Reason: The conserved checkpoint inference needs phase-specific resolution in fission yeast. PMID:12944482 reports that Rad32/Rad50/Nbs1 are required for the S-phase checkpoint but not the G2 checkpoint, whereas PMID:23080121 reports defective Chk1 signaling for a separation-of-function Mre11 allele. These assay contexts do not yet justify an unqualified G2-checkpoint assignment or a blanket rejection.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IMP PMID:7885834 Cloning and characterisation of the Schizosaccharomyces pomb...
ACCEPT
Summary: reciprocal meiotic recombination is supported.
Reason: Rad32 is required for efficient meiotic recombination and repair of meiotic DNA breaks. Removal of Rec12-linked DNA ends is a mechanistically supported contribution; the protein does not catalyze strand exchange itself.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
Summary: 3'-5'-DNA exonuclease activity is supported.
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
GO:0008311 double-stranded DNA 3'-5' DNA exonuclease activity
ISO PMID:9651580 The 3' to 5' exonuclease activity of Mre 11 facilitates repa...
ACCEPT
Summary: double-stranded DNA 3'-5' DNA exonuclease activity is supported.
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
Reason: Mre11 is the conserved phosphodiesterase nuclease of MRN. Purified homolog biochemistry establishes DNA endonuclease and 3′-to-5′ exonuclease chemistry; fission yeast catalytic-domain structures and nuclease mutants independently establish a functional nuclease. This activity is distinct from the net 5′-strand resection produced by the repair pathway.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
IDA PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: manganese ion binding is supported.
Reason: The Mre11 catalytic phosphodiesterase domain binds divalent metal ions, with manganese represented in the target-specific structural and biochemical work. Metal binding is a cofactor property of the nuclease rather than a separate physiological pathway.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Reason: The Mre11 catalytic phosphodiesterase domain binds divalent metal ions, with manganese represented in the target-specific structural and biochemical work. Metal binding is a cofactor property of the nuclease rather than a separate physiological pathway.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Reason: Fission yeast structural analysis directly resolves Mre11 dimer association with Nbs1; genetics and biochemical analysis establish Mre11 as the catalytic core of MRN.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
IDA PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: Mre11 complex is supported.
Reason: Fission yeast structural analysis directly resolves Mre11 dimer association with Nbs1; genetics and biochemical analysis establish Mre11 as the catalytic core of MRN.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
Reason: Fission yeast structural analysis directly resolves Mre11 dimer association with Nbs1; genetics and biochemical analysis establish Mre11 as the catalytic core of MRN.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
NAS PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
ACCEPT
Summary: Mre11 complex is supported.
Reason: Fission yeast structural analysis directly resolves Mre11 dimer association with Nbs1; genetics and biochemical analysis establish Mre11 as the catalytic core of MRN.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling
IBA GO_REF:0000033
ACCEPT
Summary: mitotic intra-S DNA damage checkpoint signaling is supported.
Reason: The original fission yeast study explicitly establishes the Rad32-MRN requirement for the S-phase DNA damage checkpoint. This phase-specific signaling role is experimentally grounded.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling
IMP PMID:12944482 The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is requir...
ACCEPT
Summary: mitotic intra-S DNA damage checkpoint signaling is supported.
Reason: The original fission yeast study explicitly establishes the Rad32-MRN requirement for the S-phase DNA damage checkpoint. This phase-specific signaling role is experimentally grounded.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IDA PMID:17936710 Ctp1 is a cell-cycle-regulated protein that functions with M...
ACCEPT
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location. The original PMID:17936710 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IDA PMID:19804755 Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA...
ACCEPT
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location. The original PMID:19804755 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IDA PMID:21931565 Release of Ku and MRN from DNA ends by Mre11 nuclease activi...
ACCEPT
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IDA PMID:23080121 Mre11 ATLD17/18 mutation retains Tel1/ATM activity but block...
ACCEPT
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
IDA PMID:29851556 Mre11-Rad50-dependent activity of ATM/Tel1 at DNA breaks and...
ACCEPT
Summary: site of double-strand break is supported.
Reason: The Mre11 complex binds chromosomal DNA breaks and functions in nuclear DNA repair. Target-specific recruitment and separation-of-function mutants support this cellular location.
The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure.
These activities require Mre11-Rad50, which localizes to DSBs and bind Tel1 in the absence of Nbs1.
GO:0042138 meiotic DNA double-strand break formation
IBA GO_REF:0000033
KEEP AS NON CORE
Summary: meiotic DNA double-strand break formation is retained as an ancillary annotation.
Reason: Fission yeast MRN can generate meiotic breaks at a palindrome through a Rec12-independent pathway during premeiotic replication. The experimental assertion is sound in this specialized context. Ordinary Rec12-dependent meiotic break formation does not require Rad32, so this should not imply a universal upstream requirement for programmed meiotic DSB formation.
We show that MRN-dependent DSBs are formed at or near the M-pal in vivo, and in contrast to the Rec12-dependent breaks, they appear early, during premeiotic replication.
Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts.
GO:0042138 meiotic DNA double-strand break formation
IMP PMID:15654094 A novel recombination pathway initiated by the Mre11/Rad50/N...
KEEP AS NON CORE
Summary: meiotic DNA double-strand break formation is retained as an ancillary annotation.
Reason: Fission yeast MRN can generate meiotic breaks at a palindrome through a Rec12-independent pathway during premeiotic replication. The experimental assertion is sound in this specialized context. Ordinary Rec12-dependent meiotic break formation does not require Rad32, so this should not imply a universal upstream requirement for programmed meiotic DSB formation.
We show that MRN-dependent DSBs are formed at or near the M-pal in vivo, and in contrast to the Rec12-dependent breaks, they appear early, during premeiotic replication.
Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts.
GO:0042138 meiotic DNA double-strand break formation
NAS PMID:22705791 Structure of Mre11-Nbs1 complex yields insights into ataxia-...
KEEP AS NON CORE
Summary: meiotic DNA double-strand break formation is retained as an ancillary annotation.
Reason: Fission yeast MRN can generate meiotic breaks at a palindrome through a Rec12-independent pathway during premeiotic replication. The experimental assertion is sound in this specialized context. Ordinary Rec12-dependent meiotic break formation does not require Rad32, so this should not imply a universal upstream requirement for programmed meiotic DSB formation.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
We show that MRN-dependent DSBs are formed at or near the M-pal in vivo, and in contrast to the Rec12-dependent breaks, they appear early, during premeiotic replication.
Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts.
ISO PMID:18854158 Mre11 dimers coordinate DNA end bridging and nuclease proces...
ACCEPT
Summary: DNA end binding is supported.
Reason: DNA-complex structures resolve how the conserved Mre11 dimer engages branched substrates and DNA ends. Fission yeast mutational analysis links this architecture to MRN assembly and break repair, supporting the curated orthology transfer rather than a claim of a target-only binding assay.
To define the roles of Mre11 in both DNA bridging and nucleolytic processing during initiation of DSB repair, we combined small-angle X-ray scattering (SAXS) and crystal structures of Pyrococcus furiosus Mre11 dimers bound to DNA with mutational analyses of fission yeast Mre11.
GO:0097552 mitochondrial double-strand break repair via homologous recombination
IBA GO_REF:0000033
UNDECIDED
Summary: mitochondrial double-strand break repair via homologous recombination is not fully resolved.
Reason: A mitochondrial homologous-recombination repair role is a distinct compartment-specific assertion. The reviewed fission yeast literature establishes nuclear MRN repair but does not resolve mitochondrial targeting or mitochondrial repair by Rad32. The ancestral placement underlying this IBA requires additional investigation; nuclear function alone neither validates nor refutes it.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
IDA PMID:12196391 Telomere binding of checkpoint sensor and DNA repair protein...
ACCEPT
Summary: chromosome, telomeric repeat region is supported.
Reason: Rad32 associates with fission yeast telomeres by chromatin immunoprecipitation and functions with Tel1 in telomere maintenance. Telomeric residence and maintenance are established functions of the complex.
IDA PMID:12861005 Competition between the Rad50 complex and the Ku heterodimer...
ACCEPT
Summary: chromosome, telomeric repeat region is supported.
Reason: Rad32 associates with fission yeast telomeres by chromatin immunoprecipitation and functions with Tel1 in telomere maintenance. Telomeric residence and maintenance are established functions of the complex. The original PMID:12861005 annotation is retained at its stated evidential scope; accessible source text and the independent evidence cited here are considered together.
These activities require Mre11-Rad50, which localizes to DSBs and bind Tel1 in the absence of Nbs1.
GO:1990918 double-strand break repair involved in meiotic recombination
IMP PMID:15238514 Conserved and nonconserved proteins for meiotic DNA breakage...
ACCEPT
Summary: double-strand break repair involved in meiotic recombination is supported.
Reason: Rad32 is required for efficient meiotic recombination and repair of meiotic DNA breaks. Removal of Rec12-linked DNA ends is a mechanistically supported contribution; the protein does not catalyze strand exchange itself.
Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes.
Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
Core Functions
DNA-end nuclease and coordinating subunit of MRN supporting double-strand break processing and repair.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11).
We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion.
We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops.
To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1.
MRN supports telomere maintenance and S-phase checkpoint signaling through DNA-end recognition and complex organization.
Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Mre11 DNA endonuclease, exonuclease and meiotic-cell-cycle predictions are supported but less precise than established substrate-specific activities and meiotic repair annotations.
Review rationale: DNA endonuclease activity is supported by fission yeast nuclease-mutant experiments and conserved Mre11 biochemistry. GOA already includes single-stranded DNA endonuclease activity (GO:0000014), in addition to this exact broad term. The prediction loses substrate specificity relative to that established annotation. This biological overlap does not establish training-set membership.
Supporting Evidence:
PMID:19139281: "This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11)."
PMID:9651580: "We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops."
PMID:22705791: "To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1."
PMID:9705271: "We show that the Rad50-Mre11-p95 complex possesses manganese-dependent single-stranded DNA endonuclease and 3' to 5' exonuclease activities."
Review rationale: The conserved Mre11 nuclease domain supports 3′-to-5′ exonuclease chemistry, supported by purified-protein biochemistry and fission yeast catalytic-domain structure. GOA already records double-stranded DNA 3′-5′ DNA exonuclease activity (GO:0008311) by curated orthology transfer. The predicted term omits the substrate specificity of that established function. The net polarity of DNA-end resection does not refute the intrinsic exonuclease polarity.
Supporting Evidence:
PMID:9651580: "We have investigated the enzymatic activities of the purified proteins and found that Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity, as shown by the asymmetric opening of DNA hairpin loops."
PMID:22705791: "To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1."
Review rationale: Fission yeast rad32 mutants impair meiotic recombination, and Rad32 nuclease activity is required for removal of Rec12-linked ends. These experiments establish participation in the meiotic cell cycle. GOA already captures reciprocal meiotic recombination and double-strand break repair involved in meiotic recombination, which are more informative than the broad cell-cycle term. The prediction does not imply a general requirement for Rec12-dependent break formation.
Supporting Evidence:
PMID:7885834: "Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes."
PMID:19139281: "This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11)."
PMID:15238514: "Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts."