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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 翻译后组蛋白修饰对于调节许多DNA- 模板化过程，并被认为介导染色质动力学的改变， 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细胞核功能的调控 酿酒酵母，包括转录、DNA损伤修复、有丝分裂、凋亡 和孢子形成。尽管在复制过程中对染色质的修饰仍然很差， 据了解，最近的一些研究已经描述了组蛋白H3 N-乙酰化， 末端α-螺旋（α N螺旋）在赖氨酸56作为修饰，这是重要的 在DNA复制和修复过程中维持基因组的完整性。我们在此报告 H3 Thr 45（H3-T45）的磷酸化，这是一种也位于H3 Thr 45内的组蛋白修饰， alphaN螺旋在S.酿酒。Thr 45磷酸化在DNA复制期间达到峰值， 由S期激酶Cdc 7-Dbf 4介导，作为多蛋白复合物的一部分， 本研究此外，磷酸化的H3-T45的丧失导致表型符合 复制缺陷和延长的复制应激导致H3-T45磷酸化 随着时间的积累。值得注意的是，这里描述的表型不依赖于Lys 56 乙酰化状态，以及H3的Thr 45和Lys 56的组合突变， 合成生长缺陷这些数据共同鉴定和表征了H3-T45 磷酸化作为芽殖酵母中的复制相关组蛋白修饰。

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.