Uncoupling fork speed and origin activity to identify the primary cause of replicative stress phenotypes.

ABSTRACT: In growing cells, DNA replication precedes mitotic cell division to transmit genetic information to the next generation. The slowing or stalling of DNA replication forks at natural or exogenous obstacles causes "replicative stress" that promotes genomic instability and affects cellular fitness. Replicative stress phenotypes can be characterized at the single-molecule level with DNA combing or stretched DNA fibers, but interpreting the results obtained with these approaches is complicated by the fact that the speed of replication forks is connected to the frequency of origin activation. Primary alterations in fork speed trigger secondary responses in origins, and, conversely, primary alterations in the number of active origins induce compensatory changes in fork speed. Here, by employing in

SUBMITTER: Rodriguez-Acebes S 

PROVIDER: S-EPMC6102153 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature