title: Nucleotide excision repair efficiency in quiescent human fibroblasts is modulated by circadian clock.
abstract: The efficiency of Nucleotide Excision Repair (NER)process is crucial for maintaining genomic integrity because in many organisms, including humans, it represents the only system able to repair a wide range of DNA damage. The aim of the work was to investigate whether the efficiency of the repair of photoproducts induced by UV-light is affected by the circadian phase at which irradiation occurred. NER activity has been analyzed in human quiescent fibroblasts (in the absence of the cell cycle effect), in which circadian rhythmicity has been synchronized with a pulse of dexamethasone. Our results demonstrate that both DNA damage induction and repair efficiency are strictly dependent on the phase of the circadian rhythm at which the cells are UV-exposed. Furthermore, the differences observed between fibroblasts irradiated at different circadian times (CTs) are abolished when the clock is obliterated. In addition, we observe that chromatin structure is regulated by circadian rhythmicity. Maximal chromatin relaxation occurred at the same CT when photoproduct formation and removal were highest. Our data suggest that the circadian clock regulates both the DNA sensitivity to UV damage and the efficiency of NER by controlling chromatin condensation mainly through histone acetylation.
authors: Department of Biology, University of Padova, Padova 35131, Italy.
authors: Leonardo
authors: L
authors: Bee
authors: Department of Biology, University of Padova, Padova 35131, Italy.
authors: Selena
authors: S
authors: Marini
authors: Department of Biology, University of Padova, Padova 35131, Italy.
authors: Giovanna
authors: G
authors: Pontarin
authors: Department of Biology, University of Padova, Padova 35131, Italy.
authors: Paola
authors: P
authors: Ferraro
authors: Department of Biology, University of Padova, Padova 35131, Italy.
authors: Rodolfo
authors: R
authors: Costa
authors: Department of Biology, Unit for Biochemistry, University of Fribourg, Fribourg CH-1700, Switzerland.
authors: Urs
authors: U
authors: Albrecht
authors: Department of Biology, University of Padova, Padova 35131, Italy lucia.celotti@unipd.it.
authors: Lucia
authors: L
authors: Celotti
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics*; D004260:DNA Repair; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000378:metabolism
chemical_list: D002843:Chromatin; D011740:Pyrimidine Dimers; D051760:Xeroderma Pigmentosum Group A Protein; D003907:Dexamethasone