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

Helen E. Bryant, Eva Petermann, Niklas Schultz, Ann-Sofie Jemth, Olga Loseva, Natalia Issaeva, Fredrik Johansson, Serena Fernandez, Peter McGlynn, Thomas Helleday

Research output: Contribution to journalArticlepeer-review

485 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2601-2615
Number of pages15
JournalEMBO Journal
Issue number17
Publication statusPublished - 2 Sept 2009


  • 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
  • mammalian-cells
  • damage


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