Abstract
SUMMARYTof1/Timeless protects eukaryotic cells from DNA replication stress as part of the Fork Protection Complex (FPC). Tof1 supports rapid DNA replication, fork pausing, and resolution of DNA topological stress. Here, we show that disruption of FPC function through loss of either Tof1 or Mrc1 results in DNA damage in long replicons. Despite increasing DNA damage in long replicons, loss of either Tof1 or Mrc1 concurrently reduces DNA damage in regions prone to damage caused by DNA topological stress, indicating that the rapid replication promoted by the FPC fosters completing DNA replication at the cost of increased vulnerability to DNA topological stress. Supporting this we find that atof1mutation that selectively inhibits DNA topological stress resolution increases DNA damage in contexts prone to DNA topological stress. Our data indicates that the FPC balances rapid replication with recruitment of topoisomerase I to resolve the topological stress generated by increased DNA unwinding.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献