Figure 3.

Recruitment of 53BP1 to DNA damage sites through chromatin. DSBs are recognized by the MRE11/RAD50/NBS1 (MRN) complex, which binds open DNA ends. Stable binding of the MRN complex leads to autophosphorylation of the ATM kinase, which then induces phosphorylation of the histone variant H2A.X in the vicinity of the DNA break. Phospho-H2A.X (γH2A.X) allows for accumulation of MDC1 and its partner protein RNF8, which in turn, establishes poly-ubiquitinylation of histones at the break site. 53BP1 is then stably recruited through multiple interactions, including binding to MDC1 and H4K20me2.