Unconventional effects of UVA radiation on cell cycle progression in S. pombe.
UVA radiation, the most abundant solar UV radiation reaching Earth's surface, induces oxidative stress through formation of reactive oxygen species (ROS) that can damage different cell components. Because of the broad spectrum of the possible targets of ROS, the cellular response to this radiation is complex. While extensive studies have allowed dissecting the effects of UVB, UVC and gamma radiations on cell cycle progression, few studies have dealt with the effect of UVA so far. Here we use Schizosaccharomyces pombe as a model organism to study biological effects of UVA radiation in living organisms. Through analysis of cell cycle progression in different mutant backgrounds we demonstrate that UVA delays cell cycle progression in G(2) cells in a dose dependent manner. However, despite Chk1 phosphorylation and in contrast to treatments with others genotoxic agents, this cell cycle delay is only partially dependent on DNA integrity checkpoint pathway. We also demonstrate that UVA irradiation of S phase cells slows down DNA replication in a checkpoint independent manner, activates Chk1 to prevent entry into abnormal mitosis and induces formation of Rad22 (homologue to human Rad52) foci. This indicates that DNA structure integrity is challenged. Furthermore, the cell cycle delay observed in checkpoint mutants exposed to UVA is not abolished when stress response pathway is inactivated or when down regulation of protein synthesis is prevented. In conclusion, fission yeast is a useful model to dissect the fundamental molecular mechanisms involved in UVA response that may contribute to skin cancer and aging.
Dardalhon
Delphine
D
CNRS UMR 2027, Institut Curie, Orsay, France.
Angelin
Anne Reynaud
AR
Baldacci
Giuseppe
G
Sage
Evelyne
E
Francesconi
Stefania
S
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D006918:Hydroxyurea / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects / Q000528:radiation effects; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects / Q000528:radiation effects; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects; D012568:Schizosaccharomyces / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C061178:cdc10 protein, S pombe; C085412:rad52 protein, S pombe; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; C456840:rad3 protein, S pombe; D006918:Hydroxyurea