DNA Repair in the Context of Chromatin

Modulation of chromatin is essential to nuclear processes that utilize DNA, such as transcription, replication, and repair. For example, transcription is assisted by histone post-translational modifications, as well as chromatin-remodeling complexes, which alter the structure of chromatin. Furthermore, recent advancements in the fields of DNA repair and chromatin reveal that both histone modifications and chromatin-remodeling complexes are essential for the repair of DNA lesions. In particular, chromatin-modifying complexes, such as the INO80 chromatin-remodeling complex and the Tip60 histone acetyltransferase complex, associate with the DNA damage-induced phosphorylated H2AX, which is often referred to as ?-H2AX. In S. cerevisiae, the association of INO80 with ?-H2AX is required for the recruitment of INO80 to sites of DNA double-strand breaks. Additionally, in Drosophila, Tip60 exchanges ?-H2AX for unmodified H2A in regions of DNA damage. This report reviews recent studies that emphasize the intimate relationship between evolutionarily-conserved chromatin-modifying complexes and histone post-translational modifications in the repair of DNA damage.

染色质的调节对于利用DNA的核过程至关重要，例如转录、复制和修复。例如，转录受到组蛋白翻译后修饰以及染色质重塑复合物的协助，它们会改变染色质的结构。此外，DNA修复和染色质领域的最新进展表明，组蛋白修饰和染色质重塑复合物对于DNA损伤的修复都是必不可少的。特别是，染色质修饰复合物，如INO80染色质重塑复合物和Tip60组蛋白乙酰转移酶复合物，与DNA损伤诱导的磷酸化H2AX相关联，磷酸化H2AX通常被称为γ -H2AX。在酿酒酵母中，INO80与γ -H2AX的关联是INO80募集到DNA双链断裂位点所必需的。此外，在果蝇中，Tip60在DNA损伤区域将γ -H2AX替换为未修饰的H2A。本报告综述了近期的研究，这些研究强调了在进化上保守的染色质修饰复合物和组蛋白翻译后修饰在DNA损伤修复中的密切关系。