Genomic instability in mice lacking histone H2AX.
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 H2A...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2002 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17702 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/17702 |
| Access Level: | acceso abierto |
| Palabra clave: | Chromosome Aberrations DNA Repair Recombination, Genetic Amino Acid Sequence Animals B-Lymphocytes Base Sequence Cell Cycle Cells, Cultured Cellular Senescence DNA Damage Female Gene Targeting Histones Immunoglobulin Class Switching Infertility, Male Lymphocyte Count Male Meiosis Mice Mice, Knockout Molecular Sequence Data Mutation Phosphorylation Spermatocytes T-Lymphocytes |
| Sumario: | 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. |
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