DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes.

Abstract:

:DNA double-strand breaks are generated by genotoxic agents and by cellular endonucleases as intermediates of several important physiological processes. The cellular response to genotoxic DNA breaks includes the activation of transcriptional programs known primarily to regulate cell-cycle checkpoints and cell survival. DNA double-strand breaks are generated in all developing lymphocytes during the assembly of antigen receptor genes, a process that is essential for normal lymphocyte development. Here we show that in murine lymphocytes these physiological DNA breaks activate a broad transcriptional program. This program transcends the canonical DNA double-strand break response and includes many genes that regulate diverse cellular processes important for lymphocyte development. Moreover, the expression of several of these genes is regulated similarly in response to genotoxic DNA damage. Thus, physiological DNA double-strand breaks provide cues that can regulate cell-type-specific processes not directly involved in maintaining the integrity of the genome, and genotoxic DNA breaks could disrupt normal cellular functions by corrupting these processes.

journal_name

Nature

journal_title

Nature

authors

Bredemeyer AL,Helmink BA,Innes CL,Calderon B,McGinnis LM,Mahowald GK,Gapud EJ,Walker LM,Collins JB,Weaver BK,Mandik-Nayak L,Schreiber RD,Allen PM,May MJ,Paules RS,Bassing CH,Sleckman BP

doi

10.1038/nature07392

subject

Has Abstract

pub_date

2008-12-11 00:00:00

pages

819-23

issue

7223

eissn

0028-0836

issn

1476-4687

pii

nature07392

journal_volume

456

pub_type

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