title: USF-1 is critical for maintaining genome integrity in response to UV-induced DNA photolesions.
abstract: An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations. This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents. To protect against this, cells have evolved effective mechanisms to recognize DNA damage, signal its presence, and mediate its repair. While these responses are expected to be highly regulated because they are critical to avoid human diseases, very little is known about the regulation of the expression of genes involved in mediating their effects. The Nucleotide Excision Repair (NER) is the major DNA-repair process involved in the recognition and removal of UV-mediated DNA damage. Here we use a combination of in vitro and in vivo assays with an intermittent UV-irradiation protocol to investigate the regulation of key players in the DNA-damage recognition step of NER sub-pathways (TCR and GGR). We show an up-regulation in gene expression of CSA and HR23A, which are involved in TCR and GGR, respectively. Importantly, we show that this occurs through a p53 independent mechanism and that it is coordinated by the stress-responsive transcription factor USF-1. Furthermore, using a mouse model we show that the loss of USF-1 compromises DNA repair, which suggests that USF-1 plays an important role in maintaining genomic stability.
authors.affiliation: CNRS-UMR6061 Genetic and Development Institute of Rennes, RTO Team, Rennes, France.
authors.forename: Yorann
authors.initials: Y
authors.lastname: Baron
authors.forename: Sébastien
authors.initials: S
authors.lastname: Corre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mouchet
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.forename: Sharon
authors.initials: S
authors.lastname: Prince
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Galibert
mesh_terms: D000818:Animals; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000235:genetics* / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects; D042822:Genomic Instability; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014466:Ultraviolet Rays; D051720:Upstream Stimulatory Factors / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; C083794:Hspa9 protein, mouse; C115087:Hspa9-ps1 protein, mouse; D024101:Mitochondrial Proteins; C513287:RAD23B protein, human; D034741:RNA, Small Interfering; C475578:Rad23a protein, mouse; C499250:Rad23b protein, mouse; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D004247:DNA; D045643:DNA Repair Enzymes