DNA and Chromosomes
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
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.Single-nucleotide resolution analysis of nucleotide excision repair of ribosomal DNA in humans and mice
The unique nucleolar environment, the repetitive nature of ribosomal DNA (rDNA), and especially the possible involvement of RNA polymerase I (RNAPI) in transcription-coupled repair (TCR) have made the study of repair of rDNA both interesting and challenging. TCR, the transcription-dependent, preferential excision repair of the template strand compared with the nontranscribed (coding) strand has been clearly demonstrated in genes transcribed by RNAPII. Whether TCR occurs in rDNA is unresolved. In the present work, we have applied analytical methods to map repair events in rDNA using data generated by the newly developed XR-seq procedure, which measures excision repair genome-wide with single-nucleotide resolution.Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli
Nucleotide excision repair in Escherichia coli is stimulated by transcription, specifically in the transcribed strand. Previously, it was shown that this transcription-coupled repair (TCR) is mediated by the Mfd translocase. Recently, it was proposed that in fact the majority of TCR in E. coli is catalyzed by a second pathway (“backtracking-mediated TCR”) that is dependent on the UvrD helicase and the guanosine pentaphosphate (ppGpp) alarmone/stringent response regulator. Recently, we reported that as measured by the excision repair–sequencing (XR-seq), UvrD plays no role in TCR genome-wide.
