Méndez-Acuña L, Di Tomaso M V, Palitti F, Martínez-López W
Epigenetics and Genomic Instability Laboratory, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.
Cytogenet Genome Res. 2010;128(1-3):28-36. doi: 10.1159/000296275. Epub 2010 Apr 19.
The fact that eukaryotic DNA is packed into chromatin constitutes a physical barrier to enzymes and regulatory factors to reach the DNA molecule for replication, transcription, recombination and repair. Although most studies in this field have concentrated on how chromatin regulates transcription, there is a recent emphasis on studying the role of chromatin in the response to DNA damage. Two main chromatin-remodeling mechanisms have been identified, namely, ATP-dependent chromatin-remodeling complexes and histone post-translational modifications (PTMs). PTMs constitute reversible covalent modifications in aminoacidic residues, such as serine and threonine phosphorylation, lysine acetylation, lysine and arginine methylation and lysine ubiquitylation, among others. Moreover, nucleosome composition can be modified by the incorporation of histone variants, which are assembled into nucleosomes independently of DNA replication. The phosphorylation of the histone variant H2AX (gammaH2AX) is one of the best examples of histone PTMs in response to DNA damage induction, but many others have recently been revealed. In this review, we focus on and summarize the best-known histone PTMs observed in excision repair (base excision and nucleotide excision) and double-strand break (non-homologous end-joining and homologous recombination) repair pathways. In brief, the interplay between chromatin remodelers and DNA repair factors is discussed in relation to DNA damage response mechanisms.
真核生物的DNA被包装成染色质这一事实，对酶和调控因子接触DNA分子进行复制、转录、重组和修复构成了物理障碍。尽管该领域的大多数研究都集中在染色质如何调节转录上，但最近人们开始重视研究染色质在DNA损伤应答中的作用。已确定了两种主要的染色质重塑机制，即ATP依赖的染色质重塑复合物和组蛋白翻译后修饰（PTM）。PTM是氨基酸残基上的可逆共价修饰，如丝氨酸和苏氨酸磷酸化、赖氨酸乙酰化、赖氨酸和精氨酸甲基化以及赖氨酸泛素化等。此外，核小体组成可通过组蛋白变体的掺入而改变，这些变体独立于DNA复制组装成核小体。组蛋白变体H2AX的磷酸化（γH2AX）是DNA损伤诱导后组蛋白PTM的最佳例子之一，但最近还发现了许多其他例子。在本综述中，我们重点关注并总结了在切除修复（碱基切除和核苷酸切除）和双链断裂（非同源末端连接和同源重组）修复途径中观察到的最著名的组蛋白PTM。简而言之，讨论了染色质重塑因子与DNA修复因子之间的相互作用与DNA损伤应答机制的关系。
