HISTONE H3 THR 45 PHOS IS A REPLICATION-ASSOCIATED POST-TRANSLATIONAL MOD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 翻译后的组蛋白修饰对众多DNA的调控至关重要- 模板化的过程，被认为既调节染色质动力学的变化，又调节 将效应蛋白募集到基因组的特定区域。尤其是组蛋白 丝氨酸/苏氨酸磷酸化对芽殖酵母多种核功能的调节 酿酒酵母，包括转录、DNA损伤修复、有丝分裂、凋亡 和产孢量。尽管在复制过程中对染色质的修改仍然很差 理解，最近的一些研究已经描述了组蛋白H3N- 位于Lys 56的末端α-螺旋(Alphan螺旋)作为对 在DNA复制和修复过程中保持基因组的完整性。在这里，我们报道 H3-Thr 45(H3-T45)的磷酸化，组蛋白修饰也位于H3 酿酒酵母中的Alphan螺旋。Thr-45在DNA复制过程中的磷酸化高峰，是 由S相激酶CDC7-Dbf4作为多蛋白复合体的一部分 这项研究。此外，丢失磷酸化的H3-T45会导致表型与 复制缺陷和长时间的复制应激导致H3-T45磷酸化 随着时间的推移而积累。值得注意的是，这里描述的表型与Lys 56无关 H3的乙酰化状态和Thr 45和Lys 56的组合突变引起 合成生长缺陷。这些数据共同识别和表征了H3-T45 在萌芽酵母中作为复制相关的组蛋白修饰的磷酸化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Post-translational histone modifications are crucial for the regulation of numerous DNA- templated processes, and are thought to mediate both alteration of chromatin dynamics and recruitment of effector proteins to specific regions of the genome. In particular, histone Ser/Thr phosphorylation regulates multiple nuclear functions in the budding yeast Saccharomyces cerevisiae, including transcription, DNA damage repair, mitosis, apoptosis and sporulation. Although modifications to chromatin during replication remain poorly understood, a number of recent studies have described acetylation of the histone H3 N- terminal alpha-helix (alphaN helix) at Lys 56 as a modification that is important for maintenance of genomic integrity during DNA replication and repair. Here, we report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located within the H3 alphaN helix in S. cerevisiae. Thr 45 phosphorylation peaks during DNA replication, and is mediated by the S phase kinase Cdc7-Dbf4 as part of a multiprotein complex identified in this study. Furthermore, loss of phosphorylated H3-T45 causes phenotypes consistent with replicative defects, and prolonged replication stress results in H3-T45 phosphorylation accumulation over time. Notably, the phenotypes described here are independent of Lys 56 acetylation status, and combinatorial mutations to both Thr 45 and Lys 56 of H3 cause synthetic growth defects. Together, these data identify and characterize H3-T45 phosphorylation as a replication-associated histone modification in budding yeast.