Genomic Instability in Mice Lacking Histone H2AX

2002/05/03 by Arkady Celeste, Simone Petersen, Peter Romanienko +18 · 8 citations
Biochemistry, Genetics and Molecular Biology · #DNA Repair Mechanisms #Carcinogens and Genotoxicity Assessment #Genomics and Chromatin Dynamics

paper · doi:10.1126/science.1069398

openalex publication_date 2002/05/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

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.

Citations

• DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139
• Histone H2A variants H2AX and H2AZ
• A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
• Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo

Cited by

• MDC1 is a mediator of the mammalian DNA damage checkpoint
• Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals
• Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest
• Functional Interaction of H2AX, NBS1, and p53 in ATM-Dependent DNA Damage Responses and Tumor Suppression
• BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1/S Arrest following Ionizing Radiation-induced DNA Damage
• MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks
• Epigenetic regulation of DNA repair machinery inHelicobacter pylori-induced gastric carcinogenesis
• Histone [wikipedia]