聚（ADP-核糖）聚合酶（PARP）在停滞的复制叉处被激活，以介导依赖Mre11的复制重启和重组。
PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination.
作者信息
Bryant Helen E, Petermann Eva, Schultz Niklas, Jemth Ann-Sofie, Loseva Olga, Issaeva Natalia, Johansson Fredrik, Fernandez Serena, McGlynn Peter, Helleday Thomas
机构信息
The Institute for Cancer Studies, University of Sheffield, Sheffield, UK.
出版信息
EMBO J. 2009 Sep 2;28(17):2601-15. doi: 10.1038/emboj.2009.206. Epub 2009 Jul 23.
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.
摘要
如果复制叉受到干扰，就会激活包括多种DNA修复和细胞周期检查点途径在内的多方面反应，以确保DNA复制的准确性。在此，我们表明聚（ADP-核糖）聚合酶1（PARP1）与含有小缺口的停滞复制叉结合并被其激活。PARP1与Mre11协作，在从复制阻滞中释放后促进复制叉重新启动，很可能是通过将Mre11招募到复制叉以促进DNA切除。PARP1和PARP2都是羟基脲诱导的同源重组所必需的，以促进复制阻滞后的细胞存活。总之，我们的数据表明PARP1和PARP2检测到 disrupted replication forks并吸引Mre11进行末端加工，这是后续重组修复和复制叉重新启动所必需的。
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