Abstract
In response to stress, stalled replication forks undergo fork reversal converting replication forks into a 4-way junction. FBH1 is a DNA helicase that promotes replication fork reversal. After prolonged replication stress, FBH1 promotes double strand break accumulation and cell death. One of the hallmarks of loss of fork reversal is unrestrained replication in the presence of DNA damage, but how FBH1 restrains replication at stalled forks is not known. Here, we show that FBH1 limits replication fork progression by PRIMPOL in response to hydroxyurea. However, PRIMPOL is not preventing double strand break formation in FBH1 knockout cells. Finally, we demonstrate that increased resistance of FBH1-deficient cells to hydroxyurea treatment is not due to unrestrained replication by PRIMPOL. Our results indicate FBH1 restrains PRIMPOL-mediated DNA synthesis at stalled replication forks and promoting double strand break accumulation occur by distinct mechanisms.
Full Text
The Full Text of this preprint is available as a PDF (312.2 KB). The Web version will be available soon.