Long-term, genome-wide kinetic analysis of the effect of the circadian clock and transcription on the repair of cisplatin-DNA adducts in the mouse liver.

ABSTRACT: Cisplatin is the most commonly used chemotherapeutic drug for managing solid tumors. However, toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly the Pt-d(GpG) diadduct. We recently showed that, in mice, repair of this adduct 2 h following injection is controlled by two circadian programs. 1) The circadian clock controls transcription of 2000 genes in liver and, via transcription-directed repair, controls repair of the transcribed strand (TS) of these genes in a rhythmic fashion unique to each gene's phase of transcription. 2) The excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the nontranscribed strand (NTS) and

SUBMITTER: Yang Y 

PROVIDER: S-EPMC6690688 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature