Propagation of centromeric chromatin requires exit from mitosis.

Propagation of centromeric chromatin requires exit from mitosis.
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DOI:
10.1083/jcb.200701066
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发表时间:
2007-03-12
影响因子:
7.8
通讯作者:
Cleveland, Don W.
Cleveland, Don W.
中科院分区:
生物学1区
文献类型:
--
作者:
Jansen, Lars E. T.;Black, Ben E.;Foltz, Daniel R.;Cleveland, Don W.

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着丝粒通过核化动粒的组装来指导染色体遗传,动粒是有丝分裂期间微管附着所必需的大型多蛋白复合物。人类着丝粒的特性是由表观遗传决定的,没有任何DNA序列是必要的或充分的。表观遗传标记的主要候选者是着丝粒蛋白A(CENP - A)组装进入着丝粒染色质,CENP - A是一种仅存在于功能性着丝粒的组蛋白H3变体。现在已经开发出一种使用SNAP标记的新型共价荧光脉冲追踪标记方法,并用于证明与成熟着丝粒结合的CENP - A在数量上平均分配到S期产生的姐妹着丝粒,从而在多次细胞分裂中保持稳定结合。结果表明,在复制的着丝粒DNA的百万碱基区域上加载新生的CENP - A需要经过有丝分裂,但不需要微管附着。非常令人惊讶的是,含有新的CENP - A的核小体的组装和稳定完全局限于随后的G1期,这表明有丝分裂进程与下一代着丝粒的组装/成熟之间存在直接耦合。
Centromeres direct chromosomal inheritance by nucleating assembly of the kinetochore, a large multiprotein complex required for microtubule attachment during mitosis. Centromere identity in humans is epigenetically determined, with no DNA sequence either necessary or sufficient. A prime candidate for the epigenetic mark is assembly into centromeric chromatin of centromere protein A (CENP-A), a histone H3 variant found only at functional centromeres. A new covalent fluorescent pulse-chase labeling approach using SNAP tagging has now been developed and is used to demonstrate that CENP-A bound to a mature centromere is quantitatively and equally partitioned to sister centromeres generated during S phase, thereby remaining stably associated through multiple cell divisions. Loading of nascent CENP-A on the megabase domains of replicated centromere DNA is shown to require passage through mitosis but not microtubule attachment. Very surprisingly, assembly and stabilization of new CENP-A–containing nucleosomes is restricted exclusively to the subsequent G1 phase, demonstrating direct coupling between progression through mitosis and assembly/maturation of the next generation of centromeres.
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