Vitamin D/vitamin D receptor axis regulates DNA repair during oncogene-induced senescence.

ABSTRACT: Oncogenic Ras expression is associated with activation of the DNA damage response (DDR) pathway, as evidenced by elevated DNA damage, primarily DNA double-strand breaks (DSBs), and activation of DNA damage checkpoints, which in primary human cells leads to entry into senescence. DDR activation is viewed as a physiological barrier against uncontrolled proliferation in oncogenic Ras-expressing cells, and arises in response to genotoxic stress due to the production of reactive oxygen species that damage DNA and to hyper-replication stress. Although oncogene-induced senescence (OIS) is considered a tumor suppressor mechanism, the accumulation of DNA damage in senescent cells is thought to cause genomic instability, eventually allowing secondary hits in the genome that promote tumorigenesis. To

SUBMITTER: Graziano S 

PROVIDER: S-EPMC5050051 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature