别名 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)-like 3、ADP-ribosyltransferase diphtheria toxin-like 3、ADPRT-3 + [17] |
简介 Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:25043379, PubMed:24598253, PubMed:28447610, PubMed:19354255, PubMed:23742272). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (PubMed:27530147). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). Suppresses G-quadruplex (G4) structures in response to DNA damage (PubMed:28447610). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks (PubMed:29361132, PubMed:29520010). |
作用机制 PARP1抑制剂 [+2] |
原研机构 |
最高研发阶段批准上市 |
首次获批国家/地区 美国 |
首次获批日期2016-12-19 |
靶点 |
作用机制 PARP3抑制剂 |
在研机构- |
原研机构 |
在研适应症- |
非在研适应症 |
最高研发阶段无进展 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
开始日期2025-01-16 |
申办/合作机构 NRG Oncology [+1] |
开始日期2025-01-01 |
申办/合作机构 |
开始日期2025-01-01 |
申办/合作机构 |