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

HE Bryant, E Petermann, N Schultz, AS Jemth… - The EMBO …, 2009 - embopress.org
HE Bryant, E Petermann, N Schultz, AS Jemth, O Loseva, N Issaeva, F Johansson…
The EMBO journal, 2009embopress.org
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 …
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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