Beyond heterochromatin SIR2 inhibits the initiation of DNA replication
Beyond heterochromatin SIR2 inhibits the initiation of DNA replication
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DOI：
10.4161/cc.7.21.6971
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发表时间：
2008-11-01
期刊：
影响因子：
4.3
通讯作者：
Weinreich, Michael
中科院分区：
文献类型：
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作者：
Fox, Catherine A.;Weinreich, Michael
在过去的十年中，积累的数据支持染色质结构在调节DNA复制起始及其在s期的时间方面的作用。然而，染色质结构如何影响复制起始的机制并不总是被理解。例如，在果蝇中，在一个扩增的绒毛膜位点附近的ACE3和ori - β序列上的组蛋白乙酰化与ORC（起源识别复合体）结合和该位点的再复制有关。（4,5）组蛋白乙酰化是否促进ORC结合或在复制过程中的某些后续步骤尚不清楚。在酵母中，低乙酰化的异染色质和端粒区域在s期后期复制（6,7），但限制这些位点开始复制的机制尚不完全清楚。尽管如此，似乎组蛋白乙酰化和其他类型的组蛋白修饰将显著影响DNA复制。最近发表在Molecular Cell(8)上的一项研究揭示了保守的NAD（+）依赖性组蛋白去乙酰化酶Sir2（9-13）在抑制酵母复制起始点的选择和激活所必需的多蛋白复合物的组装中的作用。在这里，我们强调了本研究的关键结论，将它们与早期工作进行比较，并概述了未来的重要问题。
Over the last decade, data have accumulated that support a role for chromatin structure in regulating the initiation of DNA replication and its timing during S-phase.(1-3) However, the mechanisms underlying how chromatin structure influences replication initiation are not always understood. For example, in Drosophila histone acetylation at the ACE3 and Ori-beta sequences near one of the amplified chorion loci is correlated with ORC ( origin recognition complex) binding and re-replication of this locus.(4,5) Whether histone acetylation promotes ORC binding or some later step in replication is not known. In yeast, hypo-acetylated heterochromatin and telomeric regions replicate late in S-phase(6,7) but the mechanisms that restrict the initiation of replication at these loci are not fully understood. Nonetheless, it seems likely that histone acetylation and other types of histone modification will significantly impact DNA replication. A recent study published in Molecular Cell(8) reveals a role for the conserved NAD(+)-dependent histone deacetylase, Sir2,(9-13) in inhibiting the assembly of the multiprotein complex necessary for the selection and activation of yeast replication origins. Here, we highlight key conclusions from this study, place them in perspective with earlier work, and outline important future questions.