EMBL Mouse Biology Unit, Via Ramarini 32, Monteorotondo, Rome, Italy.
Exp Cell Res. 2010 Jul 15;316(12):1907-13. doi: 10.1016/j.yexcr.2010.03.015. Epub 2010 Mar 25.
Constitutive heterochromatin is essential for chromosome maintenance in all eukaryotes. However, the repetitive nature of the underlying DNA, the presence of very stable protein-DNA complexes and the highly compacted nature of this type of chromatin represent a challenge for the DNA replication machinery. Data collected from different model organisms suggest that at least some of the components of the DNA replication checkpoint could be essential for ensuring the completion of DNA replication in the context of heterochromatin. I review and discuss the literature that directly or indirectly contributes to the formulation of this hypothesis. In particular, I focus my attention on Rif1, a newly discovered member of the DNA replication checkpoint. Recent data generated in mammalian cells highlight the spatial and temporal relation between Rif1, pericentromeric heterochromatin and S-phase. I review these recent and the previous data coming from studies performed in yeast in order to highlight the possible evolutionary conserved links and propose a molecular model for Rif1 role in heterochromatin replication.
组成性异染色质对于所有真核生物的染色体维持都是必不可少的。然而，潜在 DNA 的重复性质、非常稳定的蛋白质-DNA 复合物的存在以及这种类型的染色质的高度紧凑性质，对 DNA 复制机制构成了挑战。来自不同模式生物的数据表明，DNA 复制检查点的至少一些组件对于确保在异染色质背景下完成 DNA 复制是必不可少的。我回顾和讨论了直接或间接地促成这一假设的文献。特别是，我将注意力集中在 Rif1 上，这是 DNA 复制检查点的一个新发现成员。最近在哺乳动物细胞中生成的数据突出了 Rif1、着丝粒周围异染色质和 S 期之间的空间和时间关系。我回顾了这些来自酵母研究的最新数据和以前的数据，以突出可能的进化保守联系，并提出 Rif1 在异染色质复制中的分子模型。
