The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy

被引：76
|
作者：
Li, M. [1 ,2 ]
Yu, X. [2 ]
机构：
[1] Peking Univ, Hosp 3, Reprod Med Ctr, Dept Obstet & Gynecol, Beijing 100871, Peoples R China
[2] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA
来源：
ONCOGENE | 2015年 / 34卷 / 26期
关键词：
DOUBLE-STRAND BREAKS; NUCLEOTIDE EXCISION-REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; HISTONE ADP-RIBOSYLATION; HOMOLOGY-DIRECTED REPAIR; ATM PROTEIN-KINASE; DOMAIN BARD1 GENE; RING DOMAIN; POLYNUCLEOTIDE KINASE; BRCT DOMAIN;
D O I：
10.1038/onc.2014.295
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
DNA damage is a deleterious threat, but occurs daily in all types of cells. In response to DNA damage, poly(ADP-ribosyl)ation, a unique post-translational modification, is immediately catalyzed by poly(ADP-ribose) polymerases (PARPs) at DNA lesions, which facilitates DNA damage repair. Recent studies suggest that poly(ADP-ribosyl) ation is one of the first steps of cellular DNA damage response and governs early DNA damage response pathways. Suppression of DNA damage-induced poly(ADP-ribosyl) ation by PARP inhibitors impairs early DNA damage response events. Moreover, PARP inhibitors are emerging as anti-cancer drugs in phase III clinical trials for BRCA-deficient tumors. In this review, we discuss recent findings on poly(ADP-ribosyl) ation in DNA damage response as well as the molecular mechanism by which PARP inhibitors selectively kill tumor cells with BRCA mutations.
引用
收藏
页码：3349 / 3356
页数：8
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