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| Subject Categories: Genome Stability & Dynamics |
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| The EMBO Journal
(2006) 25, 5775–5782, doi:10.1038/sj.emboj.7601446 Published online 23 November 2006 |
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| ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling |
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| Thomas Stiff1, Sarah A Walker1, Karen Cerosaletti2, Aaron A Goodarzi1, Eva Petermann1, Pat Concannon2, Mark O'Driscoll1 and Penny A Jeggo1 |
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1 Genome Damage and Stability Centre, University of Sussex, Sussex, UK 2 Molecular Genetics Program, Benaroya Research Institute, Seattle, WA, USA To whom correspondence should be addressed Penny A Jeggo, Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK-East Sussex BN1 9RQ, UK. Tel.: +44 1273 678482; Fax: +44 1273 678121; E-mail: P.A.Jeggo@sussex.ac.uk Received 6 April 2006; Accepted 23 October 2006; Published online 23 November 2006. |
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| Abstract |
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| The phosphatidyl inositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) regulate parallel damage response signalling pathways. ATM is reported to be activated by DNA double-strand breaks (DSBs), whereas ATR is recruited to single-stranded regions of DNA. Although the two pathways were considered to function independently, recent studies have demonstrated that ATM functions upstream of ATR following exposure to ionising radiation (IR) in S/G2. Here, we show that ATM phosphorylation at Ser1981, a characterised autophosphorylation site, is ATR-dependent and ATM-independent following replication fork stalling or UV treatment. In contrast to IR-induced ATM-S1981 phosphorylation, UV-induced ATM-S1981 phosphorylation does not require the Nbs1 C-terminus or Mre11. ATR-dependent phosphorylation of ATM activates ATM phosphorylation of Chk2, which has an overlapping function with Chk1 in regulating G2/M checkpoint arrest. Our findings provide insight into the interplay between the PIKK damage response pathways. |
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| Keywords: ataxia telangiectasia-mutated protein, DNA damage responses, phosphorylation, PIKKs |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article Nbs1 is required for ATR-dependent phosphorylation events The EMBO Journal Article (12 Jan 2005) The EMBO Journal Article (21 Dec 2005) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks Nature Cell Biology Article (01 Jan 2006) |
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