Meta-Biol

• Pathways

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).