Fig. 2

SETD8 contributes to 53BP1 recruitment in DSBs repair. (a) Domain structure of human 53BP1. The central focus forming region (FFR) is the minimal region required for the accumulation of 53BP1, comprising the oligomerization domain (OD), a glycine–arginine-rich (GAR) motif, the tandem Tudor domain, a ubiquitin-dependent recognition (UDR) motif, and the dynein light chain (LC8) binding domain, and (b) SETD8 contributes to 53BP1 recruitment in DSBs repair. The UDR motif mediates the recruitment of 53BP1 to the nucleosomes containing H2AK15ub, while SETD8 catalyzes the methylation of histone H4K20 upon the DSBs which is bound by the tandem Tudor domain of 53BP1. In addition to catalyzing H4K20 methylation, SETD8 also interacts with the E3 ubiquitin ligases RNF8 and RNF168 to promote H2AK15ub formation in response to DSBs. Another assumption is that H4K20me2 can be increased locally by the methyltransferase MMSET which localizes at the DNA damage foci since no obvious accumulation of SUV4-20h1/2 is observed upon the DSBs