The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus
The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus
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DOI：
10.1038/ncb1845
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发表时间：
2009-03-01
影响因子：
21.3
通讯作者：
Masukata, Hisao
中科院分区：
文献类型：
--
作者：
Hayashi, Makoto T.;Takahashi, Tatsuro S.;Masukata, Hisao
异染色质是染色体结构致密的区域，其中转录和重组被失活（1，2）。DNA复制在异染色质中受到时间调控，但调控的分子机制尚未阐明。在粟酒裂殖酵母的异染色质基因座中，近着丝粒区和沉默交配型（mat）基因座在早期S期复制，而亚端粒区则不复制（3-5），表明异染色质区复制调控机制复杂。在这里，我们表明，Swi 6，一个S.粟酒裂殖酵母对应的异染色质蛋白1（HP 1），是所需的早期复制的着丝粒周围区域和MAT基因座。Swi 6刺激依赖于Dfp 1/Dbf 4依赖性激酶Cdc 7（DDK）的Sld 3的起始加载。Dfp 1内的HP 1结合基序是体外与Swi 6相互作用以及着丝粒周围区域和mat位点的早期复制所必需的。在swi 6缺陷细胞中，Dfp 1与着丝粒周围区域和mat位点的连接恢复了这些位点的早期复制。我们的研究结果表明，异染色质蛋白正调控沉默的染色质复制的启动与一个必不可少的激酶相互作用。
Heterochromatin is a structurally compacted region of chromosomes in which transcription and recombination are inactivated(1,2). DNA replication is temporally regulated in heterochromatin, but the molecular mechanism for regulation has not been elucidated. Among heterochromatin loci in Schizosaccharomyces pombe, the pericentromeric region and the silent mating-type (mat) locus replicate in early S phase, whereas the sub-telomeric region does not(3-5), suggesting complex mechanisms for regulation of replication in heterochromatic regions. Here, we show that Swi6, an S. pombe counterpart of heterochromatin protein 1 (HP1), is required for early replication of the pericentromeric region and the mat locus. Origin-loading of Sld3, which depends on Dfp1/Dbf4-dependent kinase Cdc7 (DDK), is stimulated by Swi6. An HP1-binding motif within Dfp1 is required for interaction with Swi6 in vitro and for early replication of the pericentromeric region and mat locus. Tethering of Dfp1 to the pericentromeric region and mat locus in swi6-deficient cells restores early replication of these loci. Our results show that a heterochromatic protein positively regulates initiation of replication in silenced chromatin by interacting with an essential kinase.