ATM phosphorylates histone H2AFX on S139 at DNA DSBs

Stable Identifier
R-HSA-5693549
Type
Reaction [transition]
Species
Homo sapiens
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ATM phosphorylates histone H2AFX (H2AX) on serine S139 within 1-3 minutes of double strand break (DSB) formation, producing gamma-H2AX (gamma-H2AFX) (Rogakou et al.1998, Burma et al. 2001). Basal phosphorylation of H2AFX on tyrosine residue Y142 contributes to successful S139 phosphorylation and results in a transient diphosphorylated H2AFX (Cook et al. 2009). Gamma-H2AFX localizes to a region of about 2 Mbp surrounding the site of the DSB (Rogakou et al.1998), playing an essential role in the stable recruitment of other repair proteins and formation of ionizing radiation-induced foci (IRIF) at DSB sites (Paull et al. 2000, Celeste et al. 2002, Celeste et al. 2003, Stewart et al., 2003). Recruitment of MDC1 to gamma-H2AFX may be important for the sustained phosphorylation of H2AFX at DSBs (Stewart et al. 2003).

Literature References
PubMed ID Title Journal Year
10959836 A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.

Paull, TT, Rogakou, EP, Yamazaki, V, Kirchgessner, CU, Gellert, M, Bonner, WM

Curr Biol 2000
11934988 Genomic instability in mice lacking histone H2AX

Celeste, A, Petersen, S, Romanienko, PJ, Fernandez-Capetillo, O, Chen, HT, Sedelnikova, OA, Reina-San-Martin, B, Coppola, V, Meffre, E, Difilippantonio, MJ, Redon, C, Pilch, DR, Olaru, A, Eckhaus, M, Camerini-Otero, RD, Tessarollo, L, Livak, F, Manova, K, Bonner, WM, Nussenzweig, MC, Nussenzweig, A

Science 2002
9488723 DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.

Rogakou, EP, Pilch, DR, Orr, AH, Ivanova, VS, Bonner, WM

J Biol Chem 1998
11571274 ATM phosphorylates histone H2AX in response to DNA double-strand breaks

Burma, S, Chen, BP, Murphy, M, Kurimasa, A, Chen, DJ

J Biol Chem 2001
12792649 Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks.

Celeste, A, Fernandez-Capetillo, O, Kruhlak, MJ, Pilch, DR, Staudt, DW, Lee, A, Bonner, RF, Bonner, WM, Nussenzweig, A

Nat Cell Biol 2003
19234442 Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions

Cook, PJ, Ju, BG, Telese, F, Wang, X, Glass, CK, Rosenfeld, MG

Nature 2009
Participants
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Catalyst Activity
Title
protein serine/threonine kinase activity of DNA DSBs:p-MRN:p-S-1981,Ac-K3016-ATM:KAT5:p-Y142-H2AFX-Nucleosome [nucleoplasm]
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Orthologous Events
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