@article{3935bf56ae8c4643932a17f249ebffb0,
title = "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.",
author = "Bredemeyer, {Andrea L.} and Helmink, {Beth A.} and Innes, {Cynthia L.} and Boris Calderon and McGinnis, {Lisa M.} and Mahowald, {Grace K.} and Gapud, {Eric J.} and Walker, {Laura M.} and Collins, {Jennifer B.} and Weaver, {Brian K.} and Laura Mandik-Nayak and Schreiber, {Robert D.} and Allen, {Paul M.} and May, {Michael J.} and Paules, {Richard S.} and Bassing, {Craig H.} and Sleckman, {Barry P.}",
note = "Funding Information: Acknowledgements We thank J. Bednarski, B. Van Honten and M. Diaz for critical review of the manuscript, F. W. Alt for providing us with the Artemis2/2 mice and D. Ballard for providing us with the IkBa-DN construct. This research is supported by the National Institutes of Health (NIH, grant AI47829) and the Washington University Department of Pathology and Immunology (to B.P.S.); the Department of Pathology and Center for Childhood Cancer Research of the Children{\textquoteright}s Hospital of Philadelphia, and the Abramson Family Cancer Research Institute (to C.H.B.); and the intramural research program of the NIH, National Institute of Environmental Health Sciences (to R.S.P.). B.P.S. is a recipient of a Research Scholar Award from the American Cancer Society. C.H.B. is a Pew Scholar in the Biomedical Sciences. A.L.B. is supported by a post-doctoral training grant from the NIH.",
year = "2008",
month = dec,
day = "11",
doi = "10.1038/nature07392",
language = "English (US)",
volume = "456",
pages = "819--824",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7223",
}