Regulation of replication fork progression through histone supply and demand
Regulation of replication fork progression through histone supply and demand
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DOI：
10.1126/science.1148992
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发表时间：
2007-12-21
期刊：
影响因子：
56.9
通讯作者：
Almouzni, Genevieve
中科院分区：
文献类型：
--
作者：
Groth, Anja;Corpet, Armelle;Almouzni, Genevieve
真核生物中的DNA复制需要在复制叉之前破坏核小体并在复制叉之后重新组装。一个尚未解决的问题是组蛋白动力学如何与分叉进程协调以维持染色体稳定性。在这里，我们描述了一个复杂的人组蛋白伴侣Asf 1和MCM 2 -7，假定的复制解旋酶，通过组蛋白H3-H4桥连接。RNA干扰导致的Asf 1缺失会阻碍复制位点的DNA解旋，而新组蛋白H3-H4的过度产生也会导致类似的缺陷，从而损害Asf 1的功能。这些数据链接Asf 1分子伴侣的功能，组蛋白的供应，和复制解旋的DNA染色质。我们提出Asf 1作为组蛋白受体和供体，通过Asf 1-（H3- H4）-MCM 2 - 7中间体在复制叉处处理亲本和新组蛋白，从而提供了微调复制叉进展和组蛋白供给和需求的手段。
DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-( H3- H4)- MCM2- 7 intermediate and thus provides a means to fine- tune replication fork progression and histone supply and demand.