title: E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.
abstract: Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
authors.forename: Randeep K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D045643:DNA Repair Enzymes
keywords: DNA photodamage; E2F1; epidermis; hHR23; keratinocytes