DNA damage-induced phosphorylation of a replicative DNA helicase results in inhibition of DNA replication through attenuation of helicase function.

ABSTRACT: A major function of the DNA damage responses (DDRs) that act during the replicative phase of the cell cycle is to inhibit initiation and elongation of DNA replication. It has been shown that DNA replication of the polyomavirus, SV40, is inhibited and its replication fork is slowed by cellular DDR responses. The inhibition of SV40 DNA replication is associated with enhanced DDR kinase phosphorylation of SV40 Large T-antigen (LT), the viral DNA helicase. Mass spectroscopy was used to identify a novel highly conserved DDR kinase site, T518, on LT. In cell-based assays expression of a phosphomimetic form of LT at T518 (T518D) resulted in dramatically decreased levels of SV40 DNA replication, but LT-dependent transcriptional activation was unaffected. Purified WT and LT T518D were analyzed in v

SUBMITTER: Homiski C 

PROVIDER: S-EPMC11417368 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature