PARP is activated at stalled forks to mediate Mre11‐dependent replication restart and recombination |
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| Authors: | Ann‐Sofie Jemth Olga Loseva Natalia Issaeva Fredrik Johansson Serena Fernandez Peter McGlynn Thomas Helleday |
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| Institution: | 1. Department of Genetics Microbiology and Toxicology, Stockholm University, Stockholm, Sweden;2. The Institute for Cancer Studies, University of Sheffield, Sheffield, UK;3. School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK;4. Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK |
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| 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. |
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| Keywords: | homologous recombination Mre11 poly(ADP‐ribose) polymerase replication restart stalled replication forks |
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