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Role of mammalian Mre11 in classical and alternative non-homologous end joining

The mammalian Mre11-Rad50-Nbs1 (MRN) complex coordinates double strand break (DSB) signaling with repair by homologous recombination and is associated with the H2A.X chromatin response to DSBs, but its role in non-homologous end joining (NHEJ) is less clear. Here we show that Mre11 promotes efficien...

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Detalles Bibliográficos
Autores principales: Xie, Anyong, Kwok, Amy, Scully, Ralph
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730592/
https://www.ncbi.nlm.nih.gov/pubmed/19633669
http://dx.doi.org/10.1038/nsmb.1640
Descripción
Sumario:The mammalian Mre11-Rad50-Nbs1 (MRN) complex coordinates double strand break (DSB) signaling with repair by homologous recombination and is associated with the H2A.X chromatin response to DSBs, but its role in non-homologous end joining (NHEJ) is less clear. Here we show that Mre11 promotes efficient NHEJ in both wild-type and Xrcc4(−/−) mouse embryonic stem cells. Depletion of Mre11 reduces use of microhomology during NHEJ in Xrcc4(+/+) cells and suppresses end resection in Xrcc4(−/−) cells, revealing specific roles for Mre11 in both classical and alternative NHEJ. The NHEJ function of Mre11 is independent of H2A.X. We propose a model in which both enzymatic and scaffolding functions of Mre11 cooperate to support mammalian NHEJ.