To skip or not to skip: choosing repriming to tolerate DNA damage.

To skip or not to skip: choosing repriming to tolerate DNA damage.
复制标题

跳过还是不跳过:选择重新引发以耐受DNA损伤。

DOI:
10.1016/j.molcel.2021.01.012
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发表时间:
2021-02-18
期刊:
影响因子:
16
通讯作者:
Vindigni A
Vindigni A
中科院分区:
生物学1区
文献类型:
--
作者:
Quinet A;Tirman S;Cybulla E;Meroni A;Vindigni A

文献摘要

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DNA 的精确复制不断受到内源性和外源性 DNA 损伤的威胁。专门的 DNA 复制应激反应途径可确保在存在 DNA 损伤的情况下复制叉的进展,并最大限度地减少叉伸长的延迟。这些途径广泛包括跨损伤 DNA 合成、模板转换和复制叉重新启动。在这里,我们讨论了我们对调节这些不同复制应激反应途径之间微调平衡的机制的理解的最新进展。我们还讨论了填补重新启动后在整个基因组中积累的单链 DNA 缺口所需的分子途径,以及使用重新启动而不是其他 DNA 损伤耐受途径对基因组完整性和细胞适应性的生物学后果。复制应激反应途径使 DNA 复制能够耐受障碍,并最大限度地减少叉伸长的延迟。在这篇评论中,Quinet 等人。讨论细胞选择重新启动而不是模板转换和跨损伤合成来耐受这些障碍的分子背景,以及这种选择对基因组完整性的影响。
Accurate DNA replication is constantly threatened by DNA lesions arising from endogenous and exogenous sources. Specialized DNA replication stress response pathways ensure replication fork progression in the presence of DNA lesions with minimal delay in fork elongation. These pathways broadly include translesion DNA synthesis, template switching, and replication fork repriming. Here, we discuss recent advances toward our understanding of the mechanisms that regulate the fine-tuned balance between these different replication stress response pathways. We also discuss the molecular pathways required to fill single-stranded DNA gaps that accumulate throughout the genome after repriming, and the biological consequences of using repriming instead of other DNA damage tolerance pathways on genome integrity and cell fitness. Replication stress response pathways allow DNA replication to tolerate obstacles with minimal delay in fork elongation. In this review, Quinet et al. discuss the molecular contexts in which cells choose repriming over template switching and translesion synthesis to tolerate these obstacles, and the consequences of this choice on genome integrity.
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