Mutations of the circadian clock genes Cry, Per, or Bmal1have different effects on the transcribed and nontranscribed strands of cycling genes
成果类型：
Article
署名作者：
Yang, Yanyan; Wu, Gang; Sancar, Aziz; Hogenesch, John B.
署名单位：
University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-13736
DOI：
10.1073/pnas.2316731121
发表日期：
2024-02-20
关键词：
nucleotide excision-repair
dna adduct
cisplatin
cryptochrome
architecture
mechanisms
expression
component
proteins
摘要：
One important goal of circadian medicine is to apply time- of- day dosing to improve the efficacy of chemotherapy. However, limited knowledge of how the circadian clock regulates DNA repair presents a challenge to mechanism- based clinical application. We studied time- series genome- wide nucleotide excision repair in liver and kidney of wild type and three different clock mutant genotypes (Cry1-/-Cry2-/-, Per1-/-Per2-/-, and Bmal1-/-). Rhythmic repair on the nontranscribed strand was lost in all three clock mutants. Conversely, rhythmic repair of hundreds of genes on the transcribed strand (TSs) persisted in the livers of Cry1-/-Cry2-/- and Per1-/-Per2-/- mice. We identified a tissue- specific, promoter element- driven repair mode on TSs of collagen and angio-genesis genes in the absence of clock activators or repressors. Furthermore, repair on TSs of thousands of genes was altered when the circadian clock is disrupted. These data contribute to a better understanding of the regulatory role of the circadian clock on nucleotide excision repair in mammals and may be invaluable toward the design of time- aware platinum- based interventions in cancer.