rad50 encodes the Drosophila ortholog of RAD50, the structural maintenance of chromosomes (SMC)-like ATPase subunit of the Mre11-Rad50-Nbs (MRN) complex. Rad50 has ABC-type ATPase head domains joined by a long coiled-coil with a zinc-hook dimerization motif and binds DNA ends. It regulates Mre11 nuclease activity in DSB end processing and homologous recombination repair. In Drosophila, Rad50 is distributed along mitotic chromosomes and is unstable without Mre11. With Mre11 and Nbs it caps telomeres, which Drosophila maintains by retrotransposition rather than telomerase, by promoting recruitment of HOAP and HP1. rad50 mutants show telomere fusions, chromosome breakage, accumulation of spontaneous DSBs, elevated apoptosis and pupal lethality.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000722 telomere maintenance via recombination | IBA GO_REF:0000033 | MODIFY | Summary: Telomere maintenance via recombination inherited from the RAD50 clade and mapped by ARBA. Reason: Drosophila telomere length is maintained by HeT-A/TART retrotransposition; the documented role of fly Rad50 is telomere capping (HOAP/HP1 recruitment and fusion prevention), not recombination-based telomere lengthening. The telomere-maintenance core of the inference is sound, so, as for the IMP row, it is redirected to the sibling term telomere capping (both are is_a children of telomere maintenance), consistent with the GO:0000723 rows of all three MRN subunits. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000429848 SUPPORTS SOURCE BUT NOT TARGET Yeast sources support recombination-based telomere maintenance; the Drosophila rad50 evidence among the sources concerns telomere capping (HOAP/HP1 recruitment), not recombinational telomere lengthening. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. |
| GO:0000722 telomere maintenance via recombination | IEA GO_REF:0000117 | MODIFY | Summary: Telomere maintenance via recombination inherited from the RAD50 clade and mapped by ARBA. Reason: Drosophila telomere length is maintained by HeT-A/TART retrotransposition; the documented role of fly Rad50 is telomere capping (HOAP/HP1 recruitment and fusion prevention), not recombination-based telomere lengthening. The telomere-maintenance core of the inference is sound, so, as for the IMP row, it is redirected to the sibling term telomere capping (both are is_a children of telomere maintenance), consistent with the GO:0000723 rows of all three MRN subunits. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. |
| GO:0000722 telomere maintenance via recombination | IMP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | MODIFY | Summary: rad50 mutants show telomere fusions and loss of HOAP/HP1 at telomeres. Reason: The experiment demonstrates a telomere capping defect, not a defect in recombination-based telomere maintenance; telomere capping, a sibling of recombination-based telomere maintenance under telomere maintenance, is the more accurate term. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 we demonstrate that these mutations are in the same epistasis group required for telomere capping and mitotic chromosome integrity |
| GO:0000723 telomere maintenance | IEA GO_REF:0000002 | MODIFY | Summary: The Drosophila MRN complex is required to cap telomeres and prevent end-to-end fusions, recruiting the capping proteins HOAP and HP1. Reason: Telomere maintenance is correct but general. In Drosophila, which lacks telomerase and elongates telomeres by retrotransposition, the documented MRN role is telomere capping (fusion prevention and HOAP/HP1 recruitment), so the inherited term is refined to the capping term, consistent across the three MRN subunits and with the IMP rows. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. PMID:19520832 they produce inviable embryos that succumb to failure of mitosis caused by covalent fusion of telomeric DNA |
| GO:0000723 telomere maintenance | IMP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | MODIFY | Summary: The Drosophila MRN complex is required to cap telomeres and prevent end-to-end fusions, recruiting the capping proteins HOAP and HP1. Reason: The mutant phenotype (telomere fusions and/or loss of the capping proteins HOAP and HP1 at chromosome ends) demonstrates a telomere capping defect. Drosophila lacks telomerase and maintains telomere length by retrotransposition, so the more specific capping term is the accurate one, consistent across the three MRN subunits. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. PMID:19520832 they produce inviable embryos that succumb to failure of mitosis caused by covalent fusion of telomeric DNA |
| GO:0000723 telomere maintenance | IMP PMID:16648644 The Drosophila Nbs protein functions in multiple pathways fo... | MODIFY | Summary: The Drosophila MRN complex is required to cap telomeres and prevent end-to-end fusions, recruiting the capping proteins HOAP and HP1. Reason: The mutant phenotype (telomere fusions and/or loss of the capping proteins HOAP and HP1 at chromosome ends) demonstrates a telomere capping defect. Drosophila lacks telomerase and maintains telomere length by retrotransposition, so the more specific capping term is the accurate one, consistent across the three MRN subunits. Proposed replacements: telomere capping Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. PMID:19520832 they produce inviable embryos that succumb to failure of mitosis caused by covalent fusion of telomeric DNA |
| GO:0000729 DNA double-strand break processing | NAS PMID:33556205 Drosophila telomere capping protein HOAP interacts with DSB ... | ACCEPT | Summary: MRN initiates processing (resection) of DSB ends; the NAS statement comes from a study of MRN and HOAP at telomeres. Reason: DSB end processing by the Mre11 nuclease, stimulated by Rad50 ATPase and Nbs, is the conserved biochemical role of the MRN complex. The Drosophila components act in one pathway for repair of chromosome breaks, and nbs is needed for HR gap repair. Supporting Evidence: PMID:16648644 the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000044 | ACCEPT | Summary: Rad50 acts at telomeres. Reason: Rad50 is needed for HOAP/HP1 localization at telomeres and is found along mitotic chromosomes. Supporting Evidence: PMID:15296753 This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends. |
| GO:0000793 condensed chromosome | IDA PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | ACCEPT | Summary: Rad50 immunostaining is uniformly distributed along mitotic chromosomes. Reason: Direct immunolocalization in Drosophila. Supporting Evidence: PMID:15296753 we show that this protein is uniformly distributed along mitotic chromosomes |
| GO:0000794 condensed nuclear chromosome | IBA GO_REF:0000033 | ACCEPT | Summary: Condensed nuclear chromosome inherited from the RAD50 clade. Reason: Consistent with direct observation of Rad50 on mitotic chromosomes. Supporting Evidence: PMID:15296753 we show that this protein is uniformly distributed along mitotic chromosomes |
| GO:0003690 double-stranded DNA binding | ISS PMID:15135728 Disruption of Drosophila Rad50 causes pupal lethality, the a... | ACCEPT | Summary: Double-stranded DNA binding by sequence similarity. Reason: Transferred by sequence similarity from yeast Rad50 (P12753); DNA (end) binding by the Rad50 ATPase heads within MRN is a conserved, biochemically characterised property of the Rad50 family. Fly Rad50 has not been assayed directly, but the inference is well founded. Supporting Evidence: file:DROME/rad50/rad50-deep-research-falcon.md The relevant macromolecular substrates are DNA duplexes, particularly damaged chromosome ends or DSB-associated DNA in the context of MRN |
| GO:0003691 double-stranded telomeric DNA binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Double-stranded telomeric DNA binding inherited from the RAD50 clade. Reason: The PAINT node is seeded only by budding yeast Rad50 (SGD:S000005194), whose binding is to telomerase-generated TG repeats. The term denotes binding to a telomere-specific DNA sequence, and Drosophila telomeres are retrotransposon arrays that lack such repeats and are capped in a sequence-independent manner. Fly Rad50 does act at telomeres (capping), but the sequence-specific binding activity is unlikely to apply in this lineage. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: SGD:S000005194 SUPPORTS SOURCE BUT NOT TARGET Yeast Rad50 telomeric DNA binding concerns telomerase-generated TG repeats; Drosophila telomeres are retrotransposon arrays without such repeats, so the sequence-specific activity does not carry over to fly Rad50. Supporting Evidence: file:DROME/rad50/rad50-deep-research-falcon.md Drosophila chromosome ends are maintained by specialized retrotransposons rather than the usual telomerase-based mechanism |
| GO:0005515 protein binding | IPI PMID:19520832 Mre11-Rad50-Nbs complex is required to cap telomeres during ... | REMOVE | Summary: Protein binding from co-immunoprecipitation (19520832) or a high-throughput AP-MS interactome (38944040). Reason: Generic protein binding is uninformative. The informative content (interaction among MRN subunits) is captured by the Mre11 complex annotation; removal does not imply the reported interactions are false. Supporting Evidence: PMID:19520832 the molecular defect is not the absence of MRN interaction or of Mre11 nuclease activities |
| GO:0005515 protein binding | IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f... | REMOVE | Summary: Protein binding from co-immunoprecipitation (19520832) or a high-throughput AP-MS interactome (38944040). Reason: Generic protein binding is uninformative. The informative content (interaction among MRN subunits) is captured by the Mre11 complex annotation; removal does not imply the reported interactions are false. Supporting Evidence: PMID:19520832 the molecular defect is not the absence of MRN interaction or of Mre11 nuclease activities |
| GO:0005634 nucleus | EXP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | ACCEPT | Summary: Rad50 is detected on chromosomes and in nuclei. Reason: Direct immunolocalization of Rad50. Supporting Evidence: PMID:15296753 we show that this protein is uniformly distributed along mitotic chromosomes |
| GO:0005634 nucleus | IDA PMID:33556205 Drosophila telomere capping protein HOAP interacts with DSB ... | ACCEPT | Summary: MRN components localize to the nucleus; Nbs mediates nuclear import of Mre11-Rad50. Reason: Direct localization data in Drosophila cells and conserved location of DSB repair. Supporting Evidence: PMID:33556205 Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: MRN components localize to the nucleus; Nbs mediates nuclear import of Mre11-Rad50. Reason: Direct localization data in Drosophila cells and conserved location of DSB repair. Supporting Evidence: PMID:33556205 Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus |
| GO:0005634 nucleus | IMP PMID:16648644 The Drosophila Nbs protein functions in multiple pathways fo... | ACCEPT | Summary: Rad50 accumulates in nuclei of wild-type but not nbs cells. Reason: The experiment shows nuclear localization of Rad50 that depends on Nbs. Supporting Evidence: PMID:16648644 Rad50 accumulates in the nuclei of wild-type cells but not in those of nbs cells, indicating that Nbs mediates transport of the Mre11/Rad50 complex in the nucleus |
| GO:0005694 chromosome | EXP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | ACCEPT | Summary: Rad50 localizes along mitotic chromosomes. Reason: Direct immunolocalization. Supporting Evidence: PMID:15296753 we show that this protein is uniformly distributed along mitotic chromosomes |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Rad50 localizes along mitotic chromosomes. Reason: Direct immunolocalization. Supporting Evidence: PMID:15296753 we show that this protein is uniformly distributed along mitotic chromosomes |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: rad50 mutants accumulate DNA damage and chromosome breaks. Reason: Supported by mutant phenotypes (gamma-H2Av accumulation, chromosome breakage). Supporting Evidence: PMID:15135728 This finding correlates with increased levels of phosphorylated histone H2Av, indicating an accumulation of DSBs in Rad50 mutant larvae. |
| GO:0006281 DNA repair | IMP PMID:16648644 The Drosophila Nbs protein functions in multiple pathways fo... | ACCEPT | Summary: rad50 mutants accumulate DNA damage and chromosome breaks. Reason: Supported by mutant phenotypes (gamma-H2Av accumulation, chromosome breakage). Supporting Evidence: PMID:15135728 This finding correlates with increased levels of phosphorylated histone H2Av, indicating an accumulation of DSBs in Rad50 mutant larvae. |
| GO:0006302 double-strand break repair | IBA GO_REF:0000033 | ACCEPT | Summary: The MRN complex repairs DNA double-strand breaks. Reason: Conserved core function; Drosophila mre11, rad50 and nbs mutants accumulate chromosome breaks and act in a single repair pathway. Supporting Evidence: PMID:16648644 the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations |
| GO:0006302 double-strand break repair | IEA GO_REF:0000120 | ACCEPT | Summary: The MRN complex repairs DNA double-strand breaks. Reason: Conserved core function; Drosophila mre11, rad50 and nbs mutants accumulate chromosome breaks and act in a single repair pathway. Supporting Evidence: PMID:16648644 the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations |
| GO:0006302 double-strand break repair | IMP PMID:15135728 Disruption of Drosophila Rad50 causes pupal lethality, the a... | ACCEPT | Summary: Rad50 mutant larvae accumulate DSBs and anaphase bridges. Reason: Direct mutant evidence for DSB repair, especially of replication-associated breaks. Supporting Evidence: PMID:15135728 The induction of DSBs and defects in chromosome segregation are in agreement with a role of Drosophila Rad50 in repairing the DSBs that arise during replication. |
| GO:0007004 telomere maintenance via telomerase | IBA GO_REF:0000033 | REMOVE | Summary: Telomere maintenance via telomerase inherited from the RAD50 clade. Reason: Drosophila has no telomerase; its telomeres are maintained by retrotransposition of HeT-A, TART and TAHRE elements. The telomerase-dependent process cannot occur in this organism, so this phylogenetic propagation does not apply. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000429848 SUPPORTS SOURCE BUT NOT TARGET Seeded by human RAD50 (Q92878); Drosophila has no telomerase, so telomerase-dependent telomere maintenance cannot be inherited by fly Rad50. Supporting Evidence: PMID:15296751 Since Drosophila telomeres are not added by a telomerase, our findings support an additional role for both ATM and Mre11 in telomere maintenance that is independent of telomerase regulation. |
| GO:0008104 intracellular protein localization | IMP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | MODIFY | Summary: rad50 is required for localization of HOAP and HP1 to telomeres. Reason: The phenotype is specifically loss of capping proteins from telomeres; a more precise term is protein localization to chromosome, telomeric region. Proposed replacements: protein localization to chromosome, telomeric region Supporting Evidence: PMID:15296753 Cytological analysis revealed that mutations in rad50 and mre11 drastically reduce accumulation of HOAP and HP1 at telomeres. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Rad50 ATPase activity (ABC-type head domains). Reason: ATP hydrolysis by the Rad50 head domains is the conserved catalytic activity of Rad50 and regulates Mre11 nuclease and DNA end tethering; the fly protein conserves the Walker motifs. Supporting Evidence: file:DROME/rad50/rad50-uniprot.txt Belongs to the SMC family. RAD50 subfamily. |
| GO:0016887 ATP hydrolysis activity | ISS GO_REF:0000024 | ACCEPT | Summary: Rad50 ATPase activity (ABC-type head domains). Reason: ATP hydrolysis by the Rad50 head domains is the conserved catalytic activity of Rad50 and regulates Mre11 nuclease and DNA end tethering; the fly protein conserves the Walker motifs. Supporting Evidence: file:DROME/rad50/rad50-uniprot.txt Belongs to the SMC family. RAD50 subfamily. |
| GO:0030870 Mre11 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Mre11, Rad50 and Nbs form the Drosophila MRN complex; Nbs is needed to bring Mre11-Rad50 into the nucleus and onto chromatin. Reason: Drosophila biochemical and genetic data (complex integrity, Nbs-dependent chromatin loading of MR, shared epistasis group) support membership of the Mre11 complex, consistent with the IBA and InterPro/UniRule annotations. Supporting Evidence: PMID:19520832 Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. PMID:33556205 Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. |
| GO:0030870 Mre11 complex | IDA PMID:19520832 Mre11-Rad50-Nbs complex is required to cap telomeres during ... | ACCEPT | Summary: Mre11, Rad50 and Nbs form the Drosophila MRN complex; Nbs is needed to bring Mre11-Rad50 into the nucleus and onto chromatin. Reason: Drosophila biochemical and genetic data (complex integrity, Nbs-dependent chromatin loading of MR, shared epistasis group) support membership of the Mre11 complex, consistent with the IBA and InterPro/UniRule annotations. Supporting Evidence: PMID:19520832 Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. PMID:33556205 Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. |
| GO:0030870 Mre11 complex | IEA GO_REF:0000120 | ACCEPT | Summary: Mre11, Rad50 and Nbs form the Drosophila MRN complex; Nbs is needed to bring Mre11-Rad50 into the nucleus and onto chromatin. Reason: Drosophila biochemical and genetic data (complex integrity, Nbs-dependent chromatin loading of MR, shared epistasis group) support membership of the Mre11 complex, consistent with the IBA and InterPro/UniRule annotations. Supporting Evidence: PMID:19520832 Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. PMID:33556205 Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. |
| GO:0030870 Mre11 complex | IPI PMID:19520832 Mre11-Rad50-Nbs complex is required to cap telomeres during ... | ACCEPT | Summary: Mre11, Rad50 and Nbs form the Drosophila MRN complex; Nbs is needed to bring Mre11-Rad50 into the nucleus and onto chromatin. Reason: Drosophila biochemical and genetic data (complex integrity, Nbs-dependent chromatin loading of MR, shared epistasis group) support membership of the Mre11 complex, consistent with the IBA and InterPro/UniRule annotations. Supporting Evidence: PMID:19520832 Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. PMID:33556205 Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. |
| GO:0030870 Mre11 complex | TAS PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | ACCEPT | Summary: Rad50 forms a complex with Mre11 and is unstable without it. Reason: Supported by the Rad50 instability phenotype in mre11 mutants and shared epistasis group. Supporting Evidence: PMID:15296753 Rad50 is unstable in the absence of its binding partner Mre11 |
| GO:0043047 single-stranded telomeric DNA binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Single-stranded telomeric DNA binding inherited from the RAD50 clade. Reason: As for double-stranded telomeric DNA binding - the node is seeded only by yeast Rad50 binding to telomerase-generated repeats, which Drosophila telomeres lack; no fly evidence. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: SGD:S000005194 SUPPORTS SOURCE BUT NOT TARGET Yeast Rad50 telomeric DNA binding concerns telomerase-generated TG repeats; Drosophila telomeres are retrotransposon arrays without such repeats, so the sequence-specific activity does not carry over to fly Rad50. Supporting Evidence: file:DROME/rad50/rad50-deep-research-falcon.md Drosophila chromosome ends are maintained by specialized retrotransposons rather than the usual telomerase-based mechanism |
| GO:0051276 chromosome organization | IMP PMID:15296753 The Drosophila Mre11/Rad50 complex is required to prevent bo... | KEEP AS NON CORE | Summary: mre11 and rad50 mutants show telomere fusions and chromosome breakage in mitotic cells. Reason: The chromosome aberrations reflect failed telomere capping and DSB repair; the specific roles are captured by telomere maintenance and DSB repair terms. Supporting Evidence: PMID:15296753 null mutations in the Drosophila mre11 and rad50 genes cause both telomeric fusion and chromosome breakage |
| GO:0051880 G-quadruplex DNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: G-quadruplex DNA binding inherited from the RAD50 clade. Reason: The basis is phylogenetic - the PAINT node is seeded by budding yeast Rad50 (SGD:S000005194). G-quadruplex binding is a structure-specific (not telomere-specific) property, and G4-forming sequences occur across the fly genome even though fly telomeres lack G-rich repeats, so the inheritance is not excluded. No fly Rad50 binding assay exists, so it is retained only as an inherited non-core activity on the strength of the phylogenetic inference. |
| GO:0070192 chromosome organization involved in meiotic cell cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Meiotic chromosome organization inherited from the RAD50 clade. Reason: Conserved meiotic role in other eukaryotes; not characterized for Drosophila Rad50. Supporting Evidence: PMID:15296753 This complex mediates telomere maintenance in addition to a variety of functions in response to DNA double-strand breaks |
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Download this section (compressed HTML)Q: Is Rad50 ATP hydrolysis required for MRN-dependent telomere capping in Drosophila, or only for DSB end processing?
Experiment: Express Walker A/B and signature-motif rad50 mutants in a rad50 null background and score telomere fusions, HOAP localization and gamma-H2Av foci after irradiation.
Hypothesis: Rad50 ATPase activity is dispensable for HOAP recruitment but required for DSB repair.
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Download this section (compressed HTML)rad50 (rad50) encodes a protein belonging to the SMC family and RAD50 subfamily that is involved in DNA repair. It is required for double-strand break repair and telomere maintenance.
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