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. 2021 Jun 29;12(7):1000. doi: 10.3390/genes12071000

Figure 2.

Figure 2

Upon DNA damage, L3MBTL1 and JMJD2A are released from H4K20me2 through ATM-mediated recruitment of MDC1 and phosphorylation of MDC1 at Ser 139. This leads to accumulation of RNF8 and RNF168 at DSBs, which causes ubiquitinoylation and degradation of JMJD2A by proteosome-mediated degradation and removal of L3MBTL1 by ATPase valosin-containing protein (VCP) and nuclear protein localizing cofactor protein 4 (NPL4). Thus, upon DNA damage, exposed H4K20me2 becomes available for 53BP1 binding to initiate NHEJ. 53BP1 recruits downstream effector proteins RIF1 and MAD12, which inhibit BRCA1 protein-binding to promote NHEJ over HR in the G1 phase of the cell cycle.