Bailis Julie M, Bernard Pascal, Antonelli Richard, Allshire Robin C, Forsburg Susan L
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nat Cell Biol. 2003 Dec;5(12):1111-6. doi: 10.1038/ncb1069. Epub 2003 Nov 16.
Heterochromatin performs a central role in chromosome segregation and stability by promoting cohesion at centromeres. Establishment of both heterochromatin-mediated silencing and cohesion requires passage through S phase, although the mechanism is unknown. Here we demonstrate that Schizosaccharomyces pombe Hsk1 (CDC7), a conserved Dbf4-dependent protein kinase (DDK) that regulates replication initiation, interacts with and phosphorylates the heterochromatin protein 1 (HP1) equivalent Swi6 (ref. 6). Hsk1 and its regulatory subunit Dfp1 function downstream of Swi6 localization to promote heterochromatin function and cohesion specifically at centromeres. This role for Hsk1-Dfp1 is separable from its replication initiation activity, providing a temporal link between S phase and centromere cohesion that is mediated by heterochromatin.
异染色质通过促进着丝粒处的黏连，在染色体分离和稳定性方面发挥核心作用。异染色质介导的基因沉默和黏连的建立都需要经过S期，尽管其机制尚不清楚。在这里，我们证明了粟酒裂殖酵母Hsk1（CDC7），一种保守的依赖Dbf4的蛋白激酶（DDK），它调节复制起始，与异染色质蛋白1（HP1）的同源物Swi6相互作用并使其磷酸化（参考文献6）。Hsk1及其调节亚基Dfp1在Swi6定位的下游发挥作用，以促进异染色质功能和特别是着丝粒处的黏连。Hsk1-Dfp1的这一作用与其复制起始活性是可分离的，从而在S期和由异染色质介导的着丝粒黏连之间提供了一个时间上的联系。
