S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks.

ABSTRACT: The S-phase checkpoint is involved in coupling DNA unwinding with nascent strand synthesis and is critical to maintain replication fork stability in conditions of replicative stress. However, its role in the specific regulation of leading and lagging strands at stalled forks is unclear. By conditionally depleting RNaseH2 and analyzing polymerase usage genome-wide, we examine the enzymology of DNA replication during a single S-phase in the presence of replicative stress and show that there is a differential regulation of lagging and leading strands. In checkpoint proficient cells, lagging strand replication is down-regulated through an Elg1-dependent mechanism. Nevertheless, when checkpoint function is impaired we observe a defect specifically at the leading strand, which was partially depe

SUBMITTER: Bugallo A 

PROVIDER: S-EPMC11109941 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature