Reactome | Sensing of DNA Double Strand Breaks

Sensing of DNA Double Strand Breaks

Stable Identifier

R-HSA-5693548

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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
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
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