Replication fork stalling in late S-phase elicits nascent strand degradation by DNA mismatch repair.

ABSTRACT: Eukaryotic chromosomal replication occurs in a segmented, temporal manner wherein open euchromatin and compact heterochromatin replicate during early and late S-phase respectively. Using single molecule DNA fiber analyses coupled with cell synchronization, we find that newly synthesized strands remain stable at perturbed forks in early S-phase. Unexpectedly, stalled forks are susceptible to nucleolytic digestion during late replication resulting in defective fork restart. This inherent vulnerability to nascent strand degradation is dependent on fork reversal enzymes and resection nucleases MRE11, DNA2 and EXO1. Inducing chromatin compaction elicits digestion of nascent DNA in response to fork stalling due to reduced association of RAD51 with nascent DNA. Furthermore, RAD51 occupancy at sta

SUBMITTER: Colicino-Murbach E 

PROVIDER: S-EPMC11472054 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature