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Publication : Multiple functions of MRN in end-joining pathways during isotype class switching.

First Author  Dinkelmann M Year  2009
Journal  Nat Struct Mol Biol Volume  16
Issue  8 Pages  808-13
PubMed ID  19633670 Mgi Jnum  J:272543
Mgi Id  MGI:6200200 Doi  10.1038/nsmb.1639
Citation  Dinkelmann M, et al. (2009) Multiple functions of MRN in end-joining pathways during isotype class switching. Nat Struct Mol Biol 16(8):808-13
abstractText  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.
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