Harvey Anne C, Jackson Stephen P, Downs Jessica A
Department of Biochemistry, University of Cambridge, UK.
Genetics. 2005 Jun;170(2):543-53. doi: 10.1534/genetics.104.038570. Epub 2005 Mar 21.
DNA repair takes place in the context of chromatin. Recently, it has become apparent that proteins that make up and modulate chromatin structure are involved in the detection and repair of DNA lesions. We previously demonstrated that Ser129 in the carboxyl-terminal tail of yeast histone H2A is important for double-strand-break responses. By undertaking a systematic site-directed mutagenesis approach, we identified another histone H2A serine residue (Ser122) that is important for survival in the presence of DNA-damaging agents. We show that mutation of this residue does not affect DNA damage-dependent Rad53 phosphorylation or G(2)/M checkpoint responses. Interestingly, we find that yeast lacking H2A S122 are defective in their ability to sporulate. Finally, we demonstrate that H2A S122 provides a function distinct from that of H2A S129. These data demonstrate a role for H2A S122 in facilitating survival in the presence of DNA damage and suggest a potential role in mediating homologous recombination. The distinct roles of H2A S122 and S129 in mediating these responses suggest that chromatin components can provide specialized functions for distinct DNA repair and survival mechanisms and point toward the possibility of a complex DNA damage responsive histone code.
DNA修复在染色质的环境中进行。最近,越来越明显的是,构成和调节染色质结构的蛋白质参与了DNA损伤的检测和修复。我们之前证明,酵母组蛋白H2A羧基末端尾巴上的Ser129对双链断裂反应很重要。通过采用系统的定点诱变方法,我们鉴定出另一个组蛋白H2A丝氨酸残基(Ser122),它在存在DNA损伤剂的情况下对细胞存活很重要。我们表明,该残基的突变不影响DNA损伤依赖性的Rad53磷酸化或G(2)/M期检查点反应。有趣的是,我们发现缺乏H2A S122的酵母在形成孢子的能力上存在缺陷。最后,我们证明H2A S122提供了一种不同于H2A S129的功能。这些数据证明了H2A S122在促进细胞在DNA损伤存在下存活中的作用,并暗示了其在介导同源重组中的潜在作用。H2A S122和S129在介导这些反应中的不同作用表明,染色质成分可以为不同的DNA修复和存活机制提供专门功能,并指向存在复杂的DNA损伤反应性组蛋白密码的可能性。