Sensing of DNA Double Strand Breaks

Stable Identifier
R-HSA-5693548
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Pathway
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Homo sapiens
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Detection of DNA double-strand breaks (DSBs) involves sensor proteins of the MRN complex, composed of MRE11A, RAD50 and NBN (NBS1). Binding of the MRN complex to DNA DSBs activates ATM-dependent DNA damage signaling cascade, by promoting KAT5 (Tip60) mediated acetylation of ATM and subsequent ATM autophosphorylation. Activated ATM triggers and coordinates recruitment of repair proteins to DNA DSBs (Beamish et al. 2002, Thompson and Schild 2002, Bakkenist et al. 2003, Lee and Paull 2005, Sun et al. 2005, Sun et al. 2007, Ciccia and Elledge 2010).

Literature References
PubMed ID Title Journal Year
16141325 A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM

Chen, S, Fernandes, N, Sun, Y, Jiang, X, Price, BD

Proc. Natl. Acad. Sci. U.S.A. 2005
12034743 Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM.

Kondo, N, Purdie, D, Ellis, N, Beresten, S, Gueven, N, Chen, P, Peng, C, Fukao, T, Kedar, P, Kaneko, H, Beamish, H, Lees-Miller, S, Lavin, MF

J Biol Chem 2002
17923702 DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity

Xu, Y, Sun, Y, Roy, K, Price, BD

Mol. Cell. Biol. 2007
12556884 DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation

Kastan, MB, Bakkenist, CJ

Nature 2003
20965415 The DNA damage response: making it safe to play with knives

Elledge, SJ, Ciccia, A

Mol. Cell 2010
15790808 ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex

Paull, TT, Lee, JH

Science 2005
12427531 Recombinational DNA repair and human disease.

Thompson, LH, Schild, D

Mutat Res 2002
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