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


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.

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  1. The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QN, UK.
  2. KuDOS Pharmaceuticals Ltd., Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
  3. Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK-2100, Copenhagen, Denmark.
  4. 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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