DNA double-strand breaks and ATM activation by transcription-blocking DNA lesions
Volume 9, Issue 2
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January 15, 2010
Pages 274 - 278http://dx.doi.org/10.4161/cc.9.2.10506
Authors: Olivier Sordet, Asako J. Nakamura, Christophe E. Redon and Yves Pommier View affiliations
Ataxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is a crucial mediator for the DNA double-strand break (DSB) response. We recently showed that transcription-blocking topoisomerase I cleavage complexes (TOP1cc) produce DSBs related to R-loop formation and activate ATM in post-mitotic neurons and lymphocytes. Here we discuss how TOP1cc can produce transcription arrest with R-loop formation and generate DSBs that activate ATM, as well as data suggesting that those transcription-dependent DSBs tend to form at the IgH locus and at specific genomic sites. We also address the potential roles of ATM in response to transcription-blocking TOP1cc.