NHEJ-dependent recruitment of PR-Set7 to DNA double strand breaks facilitates H4K20 methylation and 53BP1 accumulation.
Year: 2014
Type: article
Abstract: Although selective binding of 53BP1 to dimethylated histone H4 lysine 20 (H4K20me2) at DNA doublestrand breaks (DSBs) is a necessary and pivotal determinant of nonhomologous end joining (NHEJ)directed repair, the enzymes that generate H4K20me2 at DSBs were unclear.Here, we determined that the PR-Set7 monomethyltransferase (H4K20me1) regulates de novo H4K20 methylation at DSBs.Rapid recruitment of PR-Set7 to DSBs was dependent on the NHEJ Ku70 protein and necessary for NHEJ-directed repair.PR-Set7 monomethyltransferase activity was required, but insufficient, for H4K20me2 and 53BP1 nucleation at DSBs.We determined that PR-Set7-mediated H4K20me1 facilitates Suv4-20 methyltransferase recruitment and catalysis to generate H4K20me2 necessary for 53BP1 binding.The orchestrated and concerted activities of PR-Set7 and Suv4-20 were required for proficient 53BP1 nucleation and DSB repair.This report identifies PR-Set7 as an essential component of NHEJ and implicates PR-Set7 as a central determinant of NHEJ-directed repair early in mammalian DSB repair pathway choice.
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2802809908