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

HISTONE H3 THR 45 PHOS 是一种复制相关的翻译后 MOD

• 批准号: 8171472
• 负责人: PATRICK A GRANT
• 金额: $ 0.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171472
• 关键词: Acetylation; Apoptosis; Chromatin; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Repair; DNA biosynthesis; Data; Defect; Funding; Genetic Transcription; Genome; Genomics; Grant; Growth; Histone H3; Histones; Institution; Maintenance; Mediating; Mitosis; Modification; Multiprotein Complexes; Mutation; N-terminal; Nuclear; Phase; Phenotype; Phosphorylation; Phosphotransferases; Process; Proteins; Regulation; Reporting; Research; Research Personnel; Resources; Saccharomyces cerevisiae; Saccharomycetales; Source; Stress; Time; United States National Institutes of Health; alpha helix; combinatorial; histone modification; repaired; Acetylation; Apoptosis; Chromatin; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Repair; DNA biosynthesis; Data; Defect; Funding; Genetic Transcription; Genome; Genomics; Grant; Growth; Histone H3; Histones; Institution; Maintenance; Mediating; Mitosis; Modification; Multiprotein Complexes; Mutation; N-terminal; Nuclear; Phase; Phenotype; Phosphorylation; Phosphotransferases; Process; Proteins; Regulation; Reporting; Research; Research Personnel; Resources; Saccharomyces cerevisiae; Saccharomycetales; Source; Stress; Time; United States National Institutes of Health; alpha helix; combinatorial; histone modification; repaired

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 翻译后组蛋白的修饰对于调节众多DNA-至关重要 模板过程，被认为可以介导染色质动力学和 将效应蛋白募集到基因组的特定区域。特别是组蛋白 Ser/Thr磷酸化调节发芽酵母中的多个核功能 酿酒酵母，包括转录，DNA损伤修复，有丝分裂，凋亡 和孢子形。尽管在复制过程中对染色质的修饰仍然很差 理解，许多最近的研究描述了组蛋白H3 N-的乙酰化 LYS 56处的末端α-螺旋（Alphan螺旋）作为对重要的修饰，对 在DNA复制和修复过程中维持基因组完整性。在这里，我们报告 H3 THR 45（H3-T45）的磷酸化，也位于H3内的组蛋白修饰 酿酒酵母中的Alphan Helix。 THR 45在DNA复制过程中的磷酸化峰值，IS 由S期激酶CDC7-DBF4介导，作为在 这项研究。此外，磷酸化的H3-T45的损失导致表型与 复制缺陷和延长的复制应力导致H3-T45磷酸化 随着时间的推移积累。值得注意的是，此处描述的表型与Lys 56无关 H3的乙酰化状态以及对THR 45和LYS 56的组合突变 合成生长缺陷。这些数据一起识别并表征了H3-T45 磷酸化作为萌芽酵母中与复制相关的组蛋白修饰。