E3 ubiquitin-protein ligase DTX3L (DTX3L)

E3 ubiquitin-protein ligase that, in conjunction with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:26479788, PubMed:23230272). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742).

The specific role of H4K91ub1 in DNA damage response is still unclear but it may be a licensing signal for additional histone H4 post-translational modifications such as H4'Lys-20' methylation (H4K20me) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272).