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dc.contributor.authorMansour, Wael Y.
dc.contributor.authorSchumacher, Sabine
dc.contributor.authorRosskopf, Raphael
dc.contributor.authorRhein, Tim
dc.contributor.authorSchmidt-Petersen, Filip
dc.contributor.authorGatzemeier, Fruszina
dc.contributor.authorHaag, Friedrich
dc.contributor.authorBorgmann, Kerstin
dc.contributor.authorWillers, Henning
dc.contributor.authorDahm-Daphi, Jochen
dc.date.accessioned2011-02-15T00:14:28Z
dc.date.issued2008
dc.identifier.citationMansour, Wael Y., Sabine Schumacher, Raphael Rosskopf, Tim Rhein, Filip Schmidt-Petersen, Fruszina Gatzemeier, Friedrich Haag, Kerstin Borgmann, Henning Willers, and Jochen Dahm-Daphi. 2008. Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Research 36(12): 4088-4098.en_US
dc.identifier.issn0305-1048en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4725510
dc.description.abstractIn mammalian cells, DNA double-strand breaks (DSBs) are repaired by three pathways, nonhomologous end-joining (NHEJ), gene conversion (GC) and single-strand annealing (SSA). These pathways are distinct with regard to repair efficiency and mutagenic potential and must be tightly controlled to preserve viability and genomic stability. Here, we employed chromosomal reporter constructs to characterize the hierarchy of NHEJ, GC and SSA at a single I-SceI-induced DSB in Chinese hamster ovary cells. We discovered that the use of GC and SSA was increased by 6- to 8-fold upon loss of Ku80 function, suggesting that NHEJ is dominant over the other two pathways. However, NHEJ efficiency was not altered if GC was impaired by Rad51 knockdown. Interestingly, when SSA was made available as an alternative mode for DSB repair, loss of Rad51 function led to an increase in SSA activity at the expense of NHEJ, implying that Rad51 may indirectly promote NHEJ by limiting SSA. We conclude that a repair hierarchy exists to limit the access of the most mutagenic mechanism, SSA, to the break site. Furthermore, the cellular choice of repair pathways is reversible and can be influenced at the level of effector proteins such as Ku80 or Rad51.en_US
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.relation.isversionofdoi:10.1093/nar/gkn347en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475611/pdf/en_US
dash.licenseLAA
dc.titleHierarchy of Nonhomologous End-joining, Single-strand Annealing and Gene Conversion at Site-directed DNA Double-strand Breaksen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNucleic Acids Researchen_US
dash.depositing.authorWillers, Henning
dc.date.available2011-02-15T00:14:28Z
dash.affiliation.otherHMS^Radiation Oncology-Massachusetts General Hospen_US
dc.identifier.doi10.1093/nar/gkn347*
dash.contributor.affiliatedWillers, Henning


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