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| Subject Categories: Genome Stability & Dynamics |
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| The EMBO Journal
(2007) 26, 2933–2941, doi:10.1038/sj.emboj.7601733 Published online 24 May 2007 |
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| ATMIN defines an NBS1-independent pathway of ATM signalling |
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| Nnennaya Kanu and Axel Behrens |
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Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, UK To whom correspondence should be addressed Axel Behrens, Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44, Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.: +44 207 269 3361; Fax: +44 207 269 3581; E-mail: axel.behrens@cancer.org.uk Received 18 December 2006; Accepted 3 May 2007; Published online 24 May 2007. |
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| Abstract |
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| The checkpoint kinase ATM (ataxia telangiectasia mutated) transduces genomic stress signals to halt cell cycle progression and promote DNA repair in response to DNA damage. Here, we report the characterisation of an essential cofactor for ATM, ATMIN (ATM INteracting protein). ATMIN interacts with ATM through a C-terminal motif, which is also present in Nijmegen breakage syndrome (NBS)1. ATMIN and ATM colocalised in response to ATM activation by chloroquine and hypotonic stress, but not after induction of double-strand breaks by ionising radiation (IR). ATM/ATMIN complex disruption by IR was attenuated in cells with impaired NBS1 function, suggesting competition of NBS1 and ATMIN for ATM binding. ATMIN protein levels were reduced in ataxia telangiectasia cells and ATM protein levels were low in primary murine fibroblasts lacking ATMIN, indicating reciprocal stabilisation. Whereas phosphorylation of Smc1, Chk2 and p53 was normal after IR in ATMIN-deficient cells, basal ATM activity and ATM activation by hypotonic stress and inhibition of DNA replication was impaired. Thus, ATMIN defines a novel NBS1-independent pathway of ATM signalling. |
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| Keywords: ATM, ATMIN, DNA damage, NBS1 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Cell Biology News and Views (01 Jul 2005) Tudor domains track down DNA breaks Nature Cell Biology News and Views (01 Dec 2004) RESEARCHThe EMBO Journal Article (13 Dec 2006) Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting γ-H2AX induction The EMBO Journal Article (06 Sep 2006) |
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