PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination

被引：483

作者：

Bryant, Helen E. ^{[2
]}

Petermann, Eva ^{[1
]}

Schultz, Niklas ^{[3
]}

Jemth, Ann-Sofie ^{[3
]}

Loseva, Olga ^{[3
]}

Issaeva, Natalia ^{[3
]}

Johansson, Fredrik ^{[3
]}

Fernandez, Serena ^{[2
]}

McGlynn, Peter ^{[4
]}

Helleday, Thomas ^{[1
,3
]}

机构：

[1] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England

[2] Univ Sheffield, Inst Canc Studies, Sheffield, S Yorkshire, England

[3] Stockholm Univ, Dept Genet Microbiol & Toxicol, S-10691 Stockholm, Sweden

[4] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen, Scotland

来源：

EMBO JOURNAL | 2009年 / 28卷 / 17期

基金：

英国医学研究理事会; 瑞典研究理事会;

关键词：

homologous recombination; Mre11; poly(ADP-ribose) polymerase; replication restart; stalled replication forks; STRAND-BREAK REPAIR; DNA-POLYMERASE-ALPHA; DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOLS; ONCOGENE-INDUCED SENESCENCE; ADP-RIBOSE POLYMERASE; BASE EXCISION-REPAIR; HOMOLOGOUS RECOMBINATION; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; DAMAGE;

D O I：

10.1038/emboj.2009.206

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：

If replication forks are perturbed, a multifaceted response including several DNA repair and cell cycle checkpoint pathways is activated to ensure faithful DNA replication. Here, we show that poly(ADP-ribose) polymerase 1 (PARP1) binds to and is activated by stalled replication forks that contain small gaps. PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA. Both PARP1 and PARP2 are required for hydroxyurea-induced homologous recombination to promote cell survival after replication blocks. Together, our data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks. The EMBO Journal (2009) 28, 2601-2615. doi: 10.1038/emboj.2009.206; Published online 23 July 2009 Subject Categories: cell cycle; genome stability & dynamics

引用

页码：2601 / 2615

页数：15

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