Genomic instability in mice lacking histone H2AX
Genomic instability in mice lacking histone H2AX
复制标题
DOI：
10.1126/science.1069398
复制
发表时间：
2002-05-03
期刊：
影响因子：
56.9
通讯作者：
Nussenzweig, A
中科院分区：
文献类型：
--
作者：
Celeste, A;Petersen, S;Nussenzweig, A
高阶染色质结构对DNA损伤的识别和修复提出了障碍。双链断裂（DSB）诱导组蛋白H2 AX磷酸化，这与修复因子对受损DNA的募集有关。为了帮助阐明H2 AX的生理作用，我们在小鼠中靶向H2 AX。虽然H2 AX不是辐射诱导的细胞周期检查点所必需的，但H2 AX（-/-）小鼠对辐射敏感，生长迟缓，免疫缺陷，突变雄性不育。这些多效性表型与染色体不稳定、修复缺陷以及Nbs 1、53 bp 1和Brca 1（但不包括Rad 51）向辐射诱导病灶的募集受损有关。因此，H2 AX对于促进特定DNA修复复合物在受损DNA上的组装至关重要。
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.