Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 32, Issue 24, Pages 4986-4997Publisher
TAYLOR & FRANCIS INC
DOI: 10.1128/MCB.01060-12
Keywords
-
Categories
Funding
- NIH [R01 GM059321]
Ask authors/readers for more resources
Hydroxyurea (HU) treatment activates the intra-S phase checkpoint proteins Cds1 and Mrc1 to prevent replication fork collapse. We found that prolonged DNA synthesis occurs in cds1 Delta and mrc1 Delta checkpoint mutants in the presence of HU and continues after release. This is coincident with increased DNA damage measured by phosphorylated histone H2A in whole cells during release. High-resolution live-cell imaging shows that mutants first accumulate extensive replication protein A (RPA) foci, followed by increased Rad52. Both DNA synthesis and RPA accumulation require the MCM helicase. We propose that a replication fork collapse point in HU-treated cells describes the point at which accumulated DNA damage and instability at individual forks prevent further replication. After this point, cds1 Delta and mrc1 Delta forks cannot complete genome replication. These observations establish replication fork collapse as a dynamic process that continues after release from HU block.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available