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PMID: 19629035 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 28 ·No. 17 ·2009-09-02 ·Pages 2601-15

Bryant HE, Petermann E, Schultz N, Jemth AS, Loseva O, Issaeva N, Johansson F, Fernandez S, McGlynn P, Helleday T

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.

MeSH Terms
Animals Cell Cycle Proteins/metabolism Cells, Cultured Cricetinae Cricetulus DNA Repair DNA Replication/physiology DNA-Binding Proteins/metabolism Fluorescent Antibody Technique Poly(ADP-ribose) Polymerases/metabolism Recombination, Genetic/physiology
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Poly(ADP-ribose) Polymerases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Bryant Helen E
The Institute for Cancer Studies, University of Sheffield, Sheffield, UK.
Petermann Eva
Schultz Niklas
Jemth Ann-Sofie
Loseva Olga
Issaeva Natalia
Johansson Fredrik
Fernandez Serena
McGlynn Peter
Helleday Thomas
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2009.206
Published
2009-09-02
Epub
2009-00-23
Pages
2601-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2738702
Subset
IM
Grants
Medical Research Council · G0000076 · United Kingdom
Medical Research Council · G0700730 · United Kingdom
External Links
PubMed source DOI: 10.1038/emboj.2009.206 PMC Full Text View journal details
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