H2AX prevents DNA breaks from progressing to chromosome breaks and translocations.

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 Cell

journal_title

Molecular cell

authors

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 FW

doi

10.1016/j.molcel.2006.01.005

subject

Has Abstract

pub_date

2006-01-20 00:00:00

pages

201-14

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(06)00006-2

journal_volume

21

pub_type

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