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Daughter-strand gaps in DNA replication – substrates of lesion processing and initiators of distress signalling
DNA Repair ( IF 3.0 ) Pub Date : 2021-06-23 , DOI: 10.1016/j.dnarep.2021.103163
Ronald P Wong 1 , Kirill Petriukov 1 , Helle D Ulrich 1
Affiliation  

Dealing with DNA lesions during genome replication is particularly challenging because damaged replication templates interfere with the progression of the replicative DNA polymerases and thereby endanger the stability of the replisome. A variety of mechanisms for the recovery of replication forks exist, but both bacteria and eukaryotic cells also have the option of continuing replication downstream of the lesion, leaving behind a daughter-strand gap in the newly synthesized DNA. In this review, we address the significance of these single-stranded DNA structures as sites of DNA damage sensing and processing at a distance from ongoing genome replication. We describe the factors controlling the emergence of daughter-strand gaps from stalled replication intermediates, the benefits and risks of their expansion and repair via translesion synthesis or recombination-mediated template switching, and the mechanisms by which they activate local as well as global replication stress signals. Our growing understanding of daughter-strand gaps not only identifies them as targets of fundamental genome maintenance mechanisms, but also suggests that proper control over their activities has important practical implications for treatment strategies and resistance mechanisms in cancer therapy.



中文翻译:

DNA复制中的子链间隙——病变处理的底物和遇险信号的发起者

在基因组复制过程中处理 DNA 损伤特别具有挑战性,因为受损的复制模板会干扰复制 DNA 聚合酶的进程,从而危及复制体的稳定性。存在多种恢复复制叉的机制,但细菌和真核细胞也可以选择在病变下游继续复制,在新合成的 DNA 中留下子链缺口。在这篇综述中,我们讨论了这些单链 DNA 结构作为 DNA 损伤传感和处理位点的重要性,这些位点远离正在进行的基因组复制。我们描述控制女儿股的差距从停滞复制中间体,好处出现的因素及其扩修的风险通过跨损伤合成或重组介导的模板转换,以及它们激活局部和全局复制应激信号的机制。我们对子链缺口的日益了解不仅将它们确定为基本基因组维持机制的目标,而且表明对其活动的适当控制对癌症治疗的治疗策略和耐药机制具有重要的实际意义。

更新日期:2021-06-28
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