Managing Single-Stranded DNA during Replication Stress in Fission Yeast.
Managing Single-Stranded DNA during Replication Stress in Fission Yeast.
复制标题
DOI：
10.3390/biom5032123
复制
发表时间：
2015-09-18
期刊：
影响因子：
5.5
通讯作者：
Forsburg SL
中科院分区：
文献类型：
--
作者：
Sabatinos SA;Forsburg SL
复制叉停滞会产生各种反应，其中大多数会导致单链DNA的增加。ssDNA是激活细胞检查点的复制困扰的主要信号。它也是基因组不稳定性的潜在来源和突变和重组的底物。因此，管理ssDNA水平对染色体完整性至关重要。在胁迫下，野生型细胞中发生有限的ssDNA积累。相反，缺乏复制检查点的细胞不能正确地捕获叉并积累大量的ssDNA。这可能发生在复制叉聚合酶和解旋酶单元解偶联时。一些在复制解旋酶（mcm-ts）中具有突变的细胞模拟检查点缺陷细胞，并积累大量ssDNA区域以触发G2检查点。另一类解旋酶突变体（mcm 4-degron）由于解旋酶功能的立即丧失而导致S期早期的叉停滞。有趣的是，细胞意识到ssDNA存在，但未能检测到它们积累了ssDNA，并继续分裂。因此，细胞对复制停滞的反应取决于检查点活性和复制应激在S期发生的时间。在这篇综述中，我们描述的迹象，信号和症状的复制停滞从ssDNA的角度来看。我们探讨了这些影响的可能机制。我们还建议在检测和解释与ssDNA积累相关的数据时需要谨慎。
Replication fork stalling generates a variety of responses, most of which cause an increase in single-stranded DNA. ssDNA is a primary signal of replication distress that activates cellular checkpoints. It is also a potential source of genome instability and a substrate for mutation and recombination. Therefore, managing ssDNA levels is crucial to chromosome integrity. Limited ssDNA accumulation occurs in wild-type cells under stress. In contrast, cells lacking the replication checkpoint cannot arrest forks properly and accumulate large amounts of ssDNA. This likely occurs when the replication fork polymerase and helicase units are uncoupled. Some cells with mutations in the replication helicase (mcm-ts) mimic checkpoint-deficient cells, and accumulate extensive areas of ssDNA to trigger the G2-checkpoint. Another category of helicase mutant (mcm4-degron) causes fork stalling in early S-phase due to immediate loss of helicase function. Intriguingly, cells realize that ssDNA is present, but fail to detect that they accumulate ssDNA, and continue to divide. Thus, the cellular response to replication stalling depends on checkpoint activity and the time that replication stress occurs in S-phase. In this review we describe the signs, signals, and symptoms of replication arrest from an ssDNA perspective. We explore the possible mechanisms for these effects. We also advise the need for caution when detecting and interpreting data related to the accumulation of ssDNA.