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

Andrea L. Bredemeyer, Beth A. Helmink, Cynthia L. Innes, Boris Calderon, Lisa M. McGinnis, Grace K. Mahowald, Eric J. Gapud, Laura M. Walker, Jennifer B. Collins, Brian K. Weaver, Laura Mandik-Nayak, Robert D. Schreiber, Paul M. Allen, Michael J. May, Richard S. Paules, Craig H. Bassing and Barry P. Sleckman ()
Additional contact information
Andrea L. Bredemeyer: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Beth A. Helmink: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Cynthia L. Innes: Environmental Stress and Cancer Group, and NIEHS Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Boris Calderon: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Lisa M. McGinnis: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Grace K. Mahowald: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Eric J. Gapud: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Laura M. Walker: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Jennifer B. Collins: Environmental Stress and Cancer Group, and NIEHS Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Brian K. Weaver: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Laura Mandik-Nayak: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Robert D. Schreiber: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Paul M. Allen: Washington University School of Medicine, St. Louis, Missouri 63110, USA
Michael J. May: School of Veterinary Medicine, and,
Richard S. Paules: Environmental Stress and Cancer Group, and NIEHS Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Craig H. Bassing: Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Barry P. Sleckman: Washington University School of Medicine, St. Louis, Missouri 63110, USA

Nature, 2008, vol. 456, issue 7223, 819-823

Abstract: DNA breaks: there for a purpose As part of the response to exogenous DNA damage, the transcription of certain genes involved in cell cycle checkpoints and survival is affected; these changes help the cell to maintain its genomic integrity. There are also situations in which endogenous, physiological DNA double-strand breaks occur. In this work, Bredemeyer et al. show that the breaks which initiate the rearrangement of antigen receptor genes also activate a transcriptional program — but with a difference. Many of the regulated genes are involved in lymphocyte development. Thus, DNA breaks can regulate cell-type-specific processes and not just functions that will allow the cell to repair and survive a DNA break.

Date: 2008
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DOI: 10.1038/nature07392

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