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dc.contributor.authorSage, Jay M.
dc.contributor.authorGildemeister, Otto S.
dc.contributor.authorKnight, Kendall L.
dc.date2022-08-11T08:08:53.000
dc.date.accessioned2022-08-23T16:11:15Z
dc.date.available2022-08-23T16:11:15Z
dc.date.issued2010-06-18
dc.date.submitted2010-12-09
dc.identifier.citation<p>Sage, J.M., Gildemeister, O.S. and Knight, K.L. (2010) Discovery of a Novel Function for Human Rad51: Maintenance of the Mitochondrial Genome. J. Biol. Chem. 285, 18984-18990.</p>
dc.identifier.issn1083-351X
dc.identifier.doi10.1074/jbc.M109.099846
dc.identifier.pmid20413593
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33122
dc.description.abstractHomologous recombination (HR) plays a critical role in facilitating replication fork progression when the polymerase complex encounters a blocking DNA lesion, and it also serves as the primary mechanism for error-free repair of DNA double strand breaks. Rad51 is the central catalyst of HR in all eukaryotes, and to this point studies of human Rad51 have focused exclusively on events occurring within the nucleus. However, substantial amounts of HR proteins exist in the cytoplasm, yet the function of these protein pools has not been addressed. Here, we provide the first demonstration that Rad51 and the related HR proteins Rad51C and Xrcc3 exist in human mitochondria. We show stress-induced increases in both the mitochondrial levels of each protein and, importantly, the physical interaction between Rad51 and mitochondrial DNA (mtDNA). Depletion of Rad51, Rad51C, or Xrcc3 results in a dramatic decrease in mtDNA copy number as well as the complete suppression of a characteristic oxidative stress-induced copy number increase. Our results identify human mtDNA as a novel Rad51 substrate and reveal an important role for HR proteins in the maintenance of the human mitochondrial genome.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20413593&dopt=Abstract">Link to article in PubMed</p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885175/
dc.subjectCell Cycle; Cell Line, Tumor; Cytoplasm; DNA Breaks, Double-Stranded; DNA Damage; DNA, Mitochondrial; DNA-Binding Proteins; Genome; Humans; Mitochondria; Oxidative Stress; Rad51 Recombinase; Subcellular Fractions
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDiscovery of a novel function for human Rad51: maintenance of the mitochondrial genome
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume285
dc.source.issue25
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2669&amp;context=gsbs_sp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1664
dc.identifier.contextkey1680923
refterms.dateFOA2022-08-23T16:11:15Z
html.description.abstract<p>Homologous recombination (HR) plays a critical role in facilitating replication fork progression when the polymerase complex encounters a blocking DNA lesion, and it also serves as the primary mechanism for error-free repair of DNA double strand breaks. Rad51 is the central catalyst of HR in all eukaryotes, and to this point studies of human Rad51 have focused exclusively on events occurring within the nucleus. However, substantial amounts of HR proteins exist in the cytoplasm, yet the function of these protein pools has not been addressed. Here, we provide the first demonstration that Rad51 and the related HR proteins Rad51C and Xrcc3 exist in human mitochondria. We show stress-induced increases in both the mitochondrial levels of each protein and, importantly, the physical interaction between Rad51 and mitochondrial DNA (mtDNA). Depletion of Rad51, Rad51C, or Xrcc3 results in a dramatic decrease in mtDNA copy number as well as the complete suppression of a characteristic oxidative stress-induced copy number increase. Our results identify human mtDNA as a novel Rad51 substrate and reveal an important role for HR proteins in the maintenance of the human mitochondrial genome.</p>
dc.identifier.submissionpathgsbs_sp/1664
dc.contributor.departmentDepartment of Biochemistry & Molecular Pharmacology
dc.contributor.studentJay M. Sage


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