title: Genomic instability in mice lacking histone H2AX.
abstract: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Arkady
authors.initials: A
authors.lastname: Celeste
authors.forename: Simone
authors.initials: S
authors.lastname: Petersen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Romanienko
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernandez-Capetillo
authors.forename: Hua Tang
authors.initials: HT
authors.lastname: Chen
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sedelnikova
authors.forename: Bernardo
authors.initials: B
authors.lastname: Reina-San-Martin
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Coppola
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Difilippantonio
authors.forename: Christophe
authors.initials: C
authors.lastname: Redon
authors.forename: Duane R
authors.initials: DR
authors.lastname: Pilch
authors.forename: Alexandru
authors.initials: A
authors.lastname: Olaru
authors.forename: Michael
authors.initials: M
authors.lastname: Eckhaus
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Ferenc
authors.initials: F
authors.lastname: Livak
authors.forename: Katia
authors.initials: K
authors.lastname: Manova
authors.forename: William M
authors.initials: WM
authors.lastname: Bonner
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: André
authors.initials: A
authors.lastname: Nussenzweig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D001483:Base Sequence; D002453:Cell Cycle; D002478:Cells, Cultured; D016922:Cellular Senescence; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D018390:Gene Targeting; D006657:Histones / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017578:Immunoglobulin Class Switching; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology; D018655:Lymphocyte Count; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011995:Recombination, Genetic; D013090:Spermatocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
chemical_list: D006657:Histones