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dc.contributor.authorPorter-Goff, Mary Elizabeth
dc.contributor.authorRhind, Nicholas R.
dc.date2022-08-11T08:09:39.000
dc.date.accessioned2022-08-23T16:39:01Z
dc.date.available2022-08-23T16:39:01Z
dc.date.issued2009-02-13
dc.date.submitted2010-04-06
dc.identifier.citation<p>Mol Biol Cell. 2009 Apr;20(7):2096-107. Epub 2009 Feb 11. <a href="http://dx.doi.org/10.1091/mbc.E08-09-0986">Link to article on publisher's site</a></p>
dc.identifier.issn1059-1524 (Linking)
dc.identifier.doi10.1091/mbc.E08-09-0986
dc.identifier.pmid19211838
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39379
dc.description.abstractThe Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5' resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure-function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with ctp1Delta, are defective in double-strand break repair and most other functions of the complex, but they maintain an intact S phase DNA damage checkpoint. Thus, the MRN S-phase checkpoint role is separate from its Ctp1- and resection-dependent role in double-strand break repair. This observation leads us to conclude that other functions of MRN, possibly its role in replication fork metabolism, are required for S-phase DNA damage checkpoint function.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19211838&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663928/
dc.subjectChromosomal Proteins, Non-Histone
dc.subject*DNA Breaks, Double-Stranded
dc.subject*DNA Repair
dc.subjectDNA-Binding Proteins
dc.subjectExodeoxyribonucleases
dc.subjectMeiosis
dc.subjectMicrobial Viability
dc.subjectMutation
dc.subjectPhenotype
dc.subjectRecombination, Genetic
dc.subject*S Phase
dc.subjectSchizosaccharomyces
dc.subjectSchizosaccharomyces pombe Proteins
dc.subject*Signal Transduction
dc.subjectSpores, Fungal
dc.subjectTelomere
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe role of MRN in the S-phase DNA damage checkpoint is independent of its Ctp1-dependent roles in double-strand break repair and checkpoint signaling
dc.typeJournal Article
dc.source.journaltitleMolecular biology of the cell
dc.source.volume20
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2176
dc.identifier.contextkey1262956
html.description.abstract<p>The Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5' resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure-function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with ctp1Delta, are defective in double-strand break repair and most other functions of the complex, but they maintain an intact S phase DNA damage checkpoint. Thus, the MRN S-phase checkpoint role is separate from its Ctp1- and resection-dependent role in double-strand break repair. This observation leads us to conclude that other functions of MRN, possibly its role in replication fork metabolism, are required for S-phase DNA damage checkpoint function.</p>
dc.identifier.submissionpathoapubs/2176
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages2096-107


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