Abstract:
:The Mre11-Rad50-NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood. We have investigated requirements for MRN in class switch recombination (CSR), a programmed DNA rearrangement in B lymphocytes that requires NHEJ. To this end, we have engineered mice that lack the entire MRN complex in B lymphocytes or that possess an intact complex that harbors mutant Mre11 lacking DNA nuclease activities. MRN deficiency confers a strong defect in CSR, affecting both the classic and the alternative NHEJ pathways. In contrast, absence of Mre11 nuclease activities causes a milder phenotype, revealing a separation of function within the complex. We propose a model in which MRN stabilizes distant breaks and processes DNA termini to facilitate repair by both the classical and alternative NHEJ pathways.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Dinkelmann M,Spehalski E,Stoneham T,Buis J,Wu Y,Sekiguchi JM,Ferguson DOdoi
10.1038/nsmb.1639subject
Has Abstractpub_date
2009-08-01 00:00:00pages
808-13issue
8eissn
1545-9993issn
1545-9985pii
nsmb.1639journal_volume
16pub_type
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