title: H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks.
abstract: The variant histone H2AX is phosphorylated in response to UV irradiation of primary human fibroblasts in a complex fashion that is radically different from that commonly reported after DNA double-strand breaks. H2AX phosphorylation after exposure to ionizing radiation produces foci, which are detectable by immunofluorescence microscopy and have been adopted as clear and consistent quantitative markers for DNA double-strand breaks. Here we show that in contrast to ionizing radiation, UV irradiation mainly induces H2AX phosphorylation as a diffuse, even, pan-nuclear staining. UV induced pan-nuclear phosphorylation of H2AX is present in all phases of the cell cycle and is highest in S phase. H2AX phosphorylation in G(1) cells depends on nucleotide excision repair factors that may expose the S-139 site to kinase activity, is not due to DNA double-strand breaks, and plays a larger role in UV-induced signal transduction than previously realized.
authors.affiliation: Auerback Melanoma Laboratory, Room N461, Box 0808, UCSF Cancer Center, University of California-San Francisco, San Francisco, CA 94143-0808, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Marti
authors.forename: Eli
authors.initials: E
authors.lastname: Hefner
authors.forename: Luzviminda
authors.initials: L
authors.lastname: Feeney
authors.forename: Valerie
authors.initials: V
authors.lastname: Natale
authors.forename: James E
authors.initials: JE
authors.lastname: Cleaver
mesh_terms: D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D016193:G1 Phase / Q000528:radiation effects; D006657:Histones / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human