Article abstract
Nature Cell Biology 8, 37 - 45 (2005)
Published online: 4 December 2005 | doi:10.1038/ncb1337
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
Ali Jazayeri1,2,4, Jacob Falck1,4, Claudia Lukas3, Jiri Bartek3, Graeme C. M. Smith2, Jiri Lukas3 & Stephen P. Jackson1,2
Abstract
It is generally thought that the DNA-damage checkpoint kinases, ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM-dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner.
- The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QN, UK.
- KuDOS Pharmaceuticals Ltd., Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
- Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK-2100, Copenhagen, Denmark.
- These authors contributed equally to this work.
Correspondence to: Stephen P. Jackson1,2 e-mail: s.jackson@gurdon.cam.ac.uk
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