Abstract：
Homologous recombination (HR) plays an essential role in the repair of DNA double-strand breaks (DSBs), replication stress responses, and genome maintenance. However, unregulated HR during replication can impair genome duplication and compromise genome stability. The mechanisms underlying HR regulation during DNA replication are obscure. Here, we find that RTEL1 helicase, RAD51, and RAD51 paralogs are enriched at stalled replication sites. The absence of RTEL1 leads to an increase in the RAD51-mediated HR and fork reversal during replication and affects genome-wide replication, which can be rescued by co-depleting RAD51 and RAD51 paralogs. Interestingly, co-depletion of fork remodelers such as SMARCAL1/ZRANB3/HLTF/FBH1 and expression of HR-defective RAD51 mutants also rescues replication defects in RTEL1-deficient cells. The anti-recombinase function of RTEL1 during replication depends on its interaction with PCNA and helicase activity. Together, our data identify the role of RTEL1 helicase in restricting RAD51-mediated fork reversal and HR activity to facilitate error-free genome duplication.
摘要：
同源重组（HR）在DNA双链断裂（DSB）的修复中起着至关重要的作用，复制应激反应，和基因组维护。然而,复制过程中不受调节的HR会损害基因组复制并损害基因组稳定性。在DNA复制过程中HR调节的潜在机制是模糊的。这里,我们发现RTEL1解旋酶，RAD51和RAD51旁系同源物在停滞的复制站点上丰富。RTEL1的缺失导致复制过程中RAD51介导的HR和fork逆转增加，并影响全基因组复制，可以通过共同消耗RAD51和RAD51旁系同源物来拯救。有趣的是,如SMARCAL1/ZRANB3/HLTF/FBH1和HR缺陷型RAD51突变体的表达的叉子重塑体的共同消耗也拯救了RTEL1缺陷型细胞中的复制缺陷。RTEL1在复制过程中的抗重组酶功能取决于其与PCNA的相互作用和解旋酶活性。一起,我们的数据确定了RTEL1解旋酶在限制RAD51介导的叉逆转和HR活性以促进无错误基因组复制中的作用.
