DNA Replication Origins and Fork Progression at Mammalian Telomeres.
DNA Replication Origins and Fork Progression at Mammalian Telomeres.
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DOI：
10.3390/genes8040112
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发表时间：
2017-03-28
期刊：
影响因子：
3.5
通讯作者：
Yoshida K
中科院分区：
文献类型：
--
作者：
Higa M;Fujita M;Yoshida K
端粒是防止真核细胞中线性染色体临界缩短和基因组不稳定的重要染色体区域。端粒DNA的大部分以与基因组其余部分相同的方式通过半保守DNA复制进行复制。然而，最近的研究结果表明，端粒重复序列的复制是染色体不稳定的一个潜在原因，因为通过端粒的DNA复制受到阻碍复制叉的重复端粒序列和特定结构的挑战。在这篇综述中，我们总结了目前了解的机制，端粒是忠实和安全地复制在哺乳动物细胞。不同的端粒相关蛋白确保在不同的步骤中有效的端粒复制，例如复制起点的许可，复制叉的通过，复制应激后正确的叉重新启动，以及复制后结构的溶解。特别是，shelterin蛋白在端粒复制的控制中具有核心作用。通过物理相互作用，辅助蛋白被招募来维持DNA复制过程中端粒的完整性。同源复制起点和/或同源定向修复可能会挽救不适当的叉停滞或崩溃，可能会导致端粒结构和功能的缺陷。
Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions.