Li Andra, Eirín-López José M, Ausió Juan
Department of Biochemistry and Microbiology, University of Victoria, BC, Canada.
Biochem Cell Biol. 2005 Aug;83(4):505-15. doi: 10.1139/o05-114.
During the last decade, chromatin research has been focusing on the role of histone variability as a modulator of chromatin structure and function. Histone variability can be the result of either post-translational modifications or intrinsic variation at the primary structure level: histone variants. In this review, we center our attention on one of the most extensively characterized of such histone variants in recent years, histone H2AX. The molecular phylogeny of this variant seems to have run in parallel with that of the major canonical somatic H2A1 in eukaryotes. Functionally, H2AX appears to be mainly associated with maintaining the genome integrity by participating in the repair of the double-stranded DNA breaks exogenously introduced by environmental damage (ionizing radiation, chemicals) or in the process of homologous recombination during meiosis. At the structural level, these processes involve the phosphorylation of serine at the SQE motif, which is present at the very end of the C-terminal domain of H2AX, and possibly other PTMs, some of which have recently started to be defined. We discuss a model to account for how these H2AX PTMs in conjunction with chromatin remodeling complexes (such as INO80 and SWRI) can modify chromatin structure (remodeling) to support the DNA unraveling ultimately required for DNA repair.
在过去十年中，染色质研究一直聚焦于组蛋白变异性作为染色质结构和功能调节因子的作用。组蛋白变异性可能是翻译后修饰的结果，也可能是一级结构水平上的内在变异：组蛋白变体。在本综述中，我们将注意力集中在近年来特征最为广泛的此类组蛋白变体之一——组蛋白H2AX上。这种变体的分子系统发育似乎与真核生物中主要的经典体细胞H2A1并行。在功能上，H2AX似乎主要通过参与修复由环境损伤（电离辐射、化学物质）外源引入的双链DNA断裂或减数分裂期间的同源重组过程来维持基因组完整性。在结构层面，这些过程涉及H2AX C末端结构域末端存在的SQE基序处丝氨酸的磷酸化，以及可能的其他翻译后修饰，其中一些最近才开始被确定。我们讨论了一个模型，以解释这些H2AX翻译后修饰如何与染色质重塑复合物（如INO80和SWRI）一起修饰染色质结构（重塑），以支持DNA修复最终所需的DNA解旋。
