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

ABSTRACT: 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.

SUBMITTER: Bryant HE

PROVIDER: S-EPMC2738702 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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

Bryant Helen E HE Petermann Eva E Schultz Niklas N Jemth Ann-Sofie AS Loseva Olga O Issaeva Natalia N Johansson Fredrik F Fernandez Serena S McGlynn Peter P Helleday Thomas T

The EMBO journal 20090723 17

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. ...[more]

PMID: 19629035

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