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

页码：3349 / 3356

页数：8

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