Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus
Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus
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DOI：
10.1101/gad.232902
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发表时间：
2002-10-01
影响因子：
10.5
通讯作者：
Schwob, E
中科院分区：
文献类型：
--
作者：
Pasero, P;Bensimon, A;Schwob, E
真核生物如何指定其复制起点是一个尚未解答的重要问题。在这里，我们分析了酵母 rDNA 的复制组织，它由 -150 个相同的重复序列组成，每个重复序列都包含一个潜在的起源。使用 DNA 梳理和单分子成像，我们发现功能性 rDNA 起源聚集并散布在起始被沉默的大域中。这种抑制很大程度上是由 Sir2p 组蛋白脱乙酰酶介导的。 Sir2Delta 突变体中起源放电的增加导致环状 rDNA 种类的积累，这是酵母衰老的主要决定因素。我们得出的结论是，rDNA 复制受到表观遗传调控，Sir2p 可能通过抑制复制依赖性 rDNA 重组来促进基因组稳定性和寿命。
How eukaryotes specify their replication origins is an important unanswered question. Here, we analyze the replicative organization of yeast rDNA, which consists of -150 identical repeats, each containing a potential origin. Using DNA combing and single-molecule imaging, we show that functional rDNA origins are clustered and interspersed with large domains where initiation is silenced. This repression is largely mediated by the Sir2p histone-deacetylase. Increased origin firing in sir2Delta mutants leads to the accumulation of circular rDNA species, a major determinant of yeast aging. We conclude that rDNA replication is regulated epigenetically and that Sir2p may promote genome stability and longevity by suppressing replication-dependent rDNA recombination.