Genomic Instability in Mice Lacking Histone H2AX
Top Cited Papers
- 3 May 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 296 (5569) , 922-927
- https://doi.org/10.1126/science.1069398
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.Keywords
This publication has 31 references indexed in Scilit:
- AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switchingNature, 2001
- Mre11 Complex and DNA Replication: Linkage to E2F and Sites of DNA SynthesisMolecular and Cellular Biology, 2001
- Chromosomal stability and the DNA double-stranded break connectionNature Reviews Genetics, 2001
- Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in miceCurrent Biology, 2001
- Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and developmentNature, 2000
- DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformationNature, 2000
- The SCID but Not the RAG-2 Gene Product Is Required for Sμ–Sε Heavy Chain Class SwitchingImmunity, 1996
- Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.Genes & Development, 1996
- Requirement for Ku80 in growth and immunoglobulin V(D)J recombinationNature, 1996
- Atm-Deficient Mice: A Paradigm of Ataxia TelangiectasiaCell, 1996