Author: ["Stephen P. Baker","Jennifer Phillips","Scott Anderson","Qifeng Qiu","Jeffrey Shabanowitz","M. Mitchell Smith","John R. Yates 3rd","Donald F. Hunt","Patrick A. Grant"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
The S phase kinase Cdc7-Dbf4 phosphorylates histone H3 at Thr 45 during DNA replication. Phosphorylation of histone H3 at this residue is important for normal replication. 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 genome1. In particular, histone Ser/Thr phosphorylation regulates multiple nuclear functions in the budding yeast Saccharomyces cerevisiae, including transcription, DNA damage repair, mitosis, apoptosis and sporulation2. Although modifications to chromatin during replication remain poorly understood, a number of recent studies have described acetylation of the histone H3 N-terminal α-helix (αN helix) at Lys 56 as a modification that is important for maintenance of genomic integrity during DNA replication and repair3,4. Here, we report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located within the H3 αN 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.Cite this article
Baker, S., Phillips, J., Anderson, S. et al. Histone H3 Thr 45 phosphorylation is a replication-associated post-translational modification in S. cerevisiae. Nat Cell Biol 12, 294–298 (2010). https://doi.org/10.1038/ncb2030 