Moore John D, Yazgan Oya, Ataian Yeganeh, Krebs Jocelyn E
Department of Biological Sciences, University of Alaska, Anchorage, Alaska 99508, USA.
Genetics. 2007 May;176(1):15-25. doi: 10.1534/genetics.106.063792. Epub 2006 Oct 8.
There are many types of DNA damage that are repaired by a multiplicity of different repair pathways. All damage and repair occur in the context of chromatin, and histone modifications are involved in many repair processes. We have analyzed the roles of H2A and its modifications in repair by mutagenizing modifiable residues in the N- and C-terminal tails of yeast H2A and by testing strains containing these mutations in multiple DNA repair assays. We show that residues in both tails are important for homologous recombination and nonhomologous end-joining pathways of double-strand break repair, as well as for survival of UV irradiation and oxidative damage. We show that H2A serine 122 is important for repair and/or survival in each of these assays. We also observe a complex pattern of H2A phosphorylation at residues S122, T126, and S129 in response to different damage conditions. We find that overlapping but nonidentical groups of H2A residues in both tails are involved in different pathways of repair. These data suggest the presence of a set of H2A "damage codes" in which distinct patterns of modifications on both tails of H2A may be used to identify specific types of damage or to promote specific repair pathways.
存在多种类型的DNA损伤，可通过多种不同的修复途径进行修复。所有的损伤和修复都发生在染色质的背景下，并且组蛋白修饰参与许多修复过程。我们通过诱变酵母H2A的N端和C端尾巴中可修饰的残基，并在多种DNA修复试验中测试含有这些突变的菌株，分析了H2A及其修饰在修复中的作用。我们表明，两条尾巴中的残基对于双链断裂修复的同源重组和非同源末端连接途径以及紫外线照射和氧化损伤后的存活都很重要。我们表明，H2A丝氨酸122在这些试验中的每一个中对于修复和/或存活都很重要。我们还观察到，响应不同的损伤条件，H2A在残基S122、T126和S129处存在复杂的磷酸化模式。我们发现，两条尾巴中重叠但不相同的H2A残基组参与不同的修复途径。这些数据表明存在一组H2A“损伤密码”，其中H2A两条尾巴上不同的修饰模式可能用于识别特定类型的损伤或促进特定的修复途径。
