Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell. 2012 Mar 9;45(5):696-704. doi: 10.1016/j.molcel.2012.01.007. Epub 2012 Feb 9.

Replisome stability at defective DNA replication forks is independent of S phase checkpoint kinases.

Author information

1
Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 2FA, UK.

Abstract

The S phase checkpoint pathway preserves genome stability by protecting defective DNA replication forks, but the underlying mechanisms are still understood poorly. Previous work with budding yeast suggested that the checkpoint kinases Mec1 and Rad53 might prevent collapse of the replisome when nucleotide concentrations are limiting, thereby allowing the subsequent resumption of DNA synthesis. Here we describe a direct analysis of replisome stability in budding yeast cells lacking checkpoint kinases, together with a high-resolution view of replisome progression across the genome. Surprisingly, we find that the replisome is stably associated with DNA replication forks following replication stress in the absence of Mec1 or Rad53. A component of the replicative DNA helicase is phosphorylated within the replisome in a Mec1-dependent manner upon replication stress, and our data indicate that checkpoint kinases control replisome function rather than stability, as part of a multifaceted response that allows cells to survive defects in chromosome replication.

PMID:
22325992
DOI:
10.1016/j.molcel.2012.01.007
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center