Preventing replication fork collapse to maintain genome integrity.
Preventing replication fork collapse to maintain genome integrity.
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DOI：
10.1016/j.dnarep.2015.04.026
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Cortez D
中科院分区：
文献类型：
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作者：
Cortez D
数十亿个DNA碱基对在人的一生中必须被复制数万亿次。每个细胞分裂周期一次且仅一次完整和准确的复制对于维持基因组完整性和预防疾病至关重要。复制叉进展的障碍包括难以复制DNA序列，与转录的冲突以及DNA损伤进一步增加了基因组维护的挑战。这些障碍经常会导致fork停滞，但很少会导致无法完成复制。强大的机制确保停滞分叉保持稳定，能够恢复DNA合成或被聚合分叉拯救。然而，当失败发生时，分叉会崩溃，导致基因组重排、细胞死亡和疾病。尽管人们对此非常感兴趣，但修复受损复制分叉、稳定它们并确保成功复制的机制仍然只是部分了解。人们提出了不同的叉折模型，对DNA和复制体发生的情况有不同的描述。在这里，我将定义叉崩溃，并描述关于复制检查点如何阻止它维持基因组稳定性的已知信息。
Billions of base pairs of DNA must be replicated trillions of times in a human lifetime. Complete and accurate replication once and only once per cell division cycle is essential to maintain genome integrity and prevent disease. Impediments to replication fork progression including difficult to replicate DNA sequences, conflicts with transcription, and DNA damage further add to the genome maintenance challenge. These obstacles frequently cause fork stalling, but only rarely cause a failure to complete replication. Robust mechanisms ensure that stalled forks remain stable and capable of either resuming DNA synthesis or being rescued by converging forks. However, when failures do happen the fork collapses leading to genome rearrangements, cell death and disease. Despite intense interest, the mechanisms to repair damaged replication forks, stabilize them, and ensure successful replication remain only partly understood. Different models of fork collapse have been proposed with varying descriptions of what happens to the DNA and replisome. Here, I will define fork collapse and describe what is known about how the replication checkpoint prevents it to maintain genome stability.