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. Author manuscript; available in PMC: 2013 Dec 31.
Published in final edited form as: Cancer Lett. 2011 Dec 21;327(1-2):123–133. doi: 10.1016/j.canlet.2011.12.025

Figure 1.

Figure 1

γ-H2AX formation and its role in the irradiation-induced DNA repair foci. The foci assembly is a hierarchical process which starts with the DSB recognition by the MRN (MRE11-RAD50-NBS1) complex, recruitment of the ATM kinase and its autophosphorylation at the DSB site. The resulting ATM-mediated phosphorylation of H2AX (γ-H2AX) allows the recruitment of MDC1. MDC1 binding to γ-H2AX, in turn, allows the enrollment of other proteins including the MRN complex and ATM. Additional recruitment of ATM will then permit accrued phosphorylation of H2AX and other DNA repair proteins concentrating at the DSB (RNF8, BRCA1, 53BP1, etc.). MDC1 also recruits RNF8, an ubiquitin ligase which initiates histone H2 (H2AX, H2A, H2B) poly-ubiquitylation at DSB sites. These histone modifications allocate a second wave of protein accumulation, including proteins and/or protein complexes such as the BRCA1 A complex, 53BP1, RAD18, PTIP, EXPAND1, etc. γ-H2AX is also involved in the recruitment of chromatin remodeling complexes and chromatid cohesins. Foci formation is thought to stimulate DNA repair and checkpoint activation, to allow chromatin remodeling and sister chromatid cohesion and to facilitate cohesion of broken chromosome ends. P: phosphate, Ub: ubiquitin, me: methyl, M: MRE11, N: NBS1, R: RAD50. To simplify, single histones are shown.