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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bee L,Marini S,Pontarin G,Ferraro P,Costa R,Albrecht U,Celotti L

doi

10.1093/nar/gkv081

subject

Has Abstract

pub_date

2015-02-27 00:00:00

pages

2126-37

issue

4

eissn

0305-1048

issn

1362-4962

pii

gkv081

journal_volume

43

pub_type

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