Abstract:
:The mammalian protein 53BP1 is activated in many cell types in response to genotoxic stress, including DNA double-strand breaks (DSBs). We now examine potential functions for 53BP1 in the specific genomic alterations that occur in B lymphocytes. Although 53BP1 was dispensable for V(D)J recombination and somatic hypermutation (SHM), the processes by which immunoglobulin (Ig) variable region exons are assembled and mutated, it was required for Igh class-switch recombination (CSR), the recombination and deletion process by which Igh constant region genes are exchanged. When stimulated to undergo CSR, 53BP1-deficient cells exhibited no defect in C(H) germline transcription or AID expression, however these cells had a profound decrease in switch junctions. The current findings, in combination with the known 53BP1 functions and how it is activated, implicate the DNA damage response to DSBs in the joining phase of class-switch recombination.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Manis JP,Morales JC,Xia Z,Kutok JL,Alt FW,Carpenter PBdoi
10.1038/ni1067keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
481-7issue
5eissn
1529-2908issn
1529-2916pii
ni1067journal_volume
5pub_type
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