Abstract:
:Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks occur at high frequency in primary H2AX-deficient B cells activated for CSR and that a substantial proportion of these breaks participate in chromosomal translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations. Thus, our findings implicate a general role for these factors in promoting end joining and thereby preventing DSBs from progressing into chromosomal breaks and translocations. As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations.
journal_name
Mol Celljournal_title
Molecular cellauthors
Franco S,Gostissa M,Zha S,Lombard DB,Murphy MM,Zarrin AA,Yan C,Tepsuporn S,Morales JC,Adams MM,Lou Z,Bassing CH,Manis JP,Chen J,Carpenter PB,Alt FWdoi
10.1016/j.molcel.2006.01.005subject
Has Abstractpub_date
2006-01-20 00:00:00pages
201-14issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(06)00006-2journal_volume
21pub_type
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