Increased global transcription activity as a mechanism of replication stress in cancer.

ABSTRACT: Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS^V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS^V12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore,

SUBMITTER: Kotsantis P 

PROVIDER: S-EPMC5062618 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature