期刊
NATURE CELL BIOLOGY
卷 12, 期 3, 页码 294-U103出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2030
关键词
-
类别
资金
- NIH [5 T32 CA009109-30, 5 P30 CA044579-18, R56 DK082673-01, GM37537, P41 RR011823, GM60444]
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(1). 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(2). 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 (alpha N helix) at Lys 56 as a modification that is important for maintenance of genomic integrity during DNA replication and repair(3,4). Here, we report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located within the H3 alpha N 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据