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Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
DNA Repair ( IF 3.8 ) Pub Date : 2020-06-18 , DOI: 10.1016/j.dnarep.2020.102900
Guido Zagnoli-Vieira 1 , Keith W Caldecott 2
Affiliation  

DNA topoisomerases alleviate the torsional stress that is generated by processes that are central to genome metabolism such as transcription and DNA replication. To do so, these enzymes generate an enzyme intermediate known as the cleavage complex in which the topoisomerase is covalently linked to the termini of a DNA single- or double-strand break. Whilst cleavage complexes are normally transient they can occasionally become abortive, creating protein-linked DNA breaks that threaten genome stability and cell survival; a process promoted and exploited in the cancer clinic by the use of topoisomerase ‘poisons’. Here, we review the consequences to genome stability and human health of abortive topoisomerase-induced DNA breakage and the cellular pathways that cells have adopted to mitigate them, with particular focus on an important class of enzymes known as tyrosyl-DNA phosphodiesterases.



中文翻译:

用酪氨酰-DNA磷酸二酯酶解开捕获的拓扑异构酶。

DNA拓扑异构酶可减轻由基因组新陈代谢至关重要的过程(如转录和DNA复制)产生的扭转应力。为此,这些酶产生一种称为酶切复合物的酶中间体,其中拓扑异构酶与DNA单链或双链断裂的末端共价连接。尽管裂解复合物通常是瞬时的,但它们有时可能会流产,产生与蛋白质相关的DNA断裂,从而威胁基因组稳定性和细胞存活。通过使用拓扑异构酶“毒药”在癌症诊所促进和开发的过程。在这里,我们回顾了流产的拓扑异构酶诱导的DNA断裂对基因组稳定性和人类健康的影响,以及细胞为缓解这些断裂所采取的细胞途径,

更新日期:2020-07-10
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