Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, U.K.
Essays Biochem. 2020 Oct 26;64(5):819-830. doi: 10.1042/EBC20200012.
Helicases are enzymes that use the energy derived from ATP hydrolysis to catalyze the unwinding of DNA or RNA. The RecQ family of helicases is conserved through evolution from prokaryotes to higher eukaryotes and plays important roles in various DNA repair pathways, contributing to the maintenance of genome integrity. Despite their roles as general tumor suppressors, there is now considerable interest in exploiting RecQ helicases as synthetic lethal targets for the development of new cancer therapeutics. In this review, we summarize the latest developments in the structural and mechanistic study of RecQ helicases and discuss their roles in various DNA repair pathways. Finally, we consider the potential to exploit RecQ helicases as therapeutic targets and review the recent progress towards the development of small molecules targeting RecQ helicases as cancer therapeutics.
解旋酶是利用 ATP 水解产生的能量来催化 DNA 或 RNA 解旋的酶。RecQ 解旋酶家族在从原核生物到高等真核生物的进化过程中得到了保守，在各种 DNA 修复途径中发挥着重要作用，有助于维持基因组的完整性。尽管它们作为一般肿瘤抑制因子发挥作用，但现在人们对利用 RecQ 解旋酶作为合成致死靶点来开发新的癌症治疗方法产生了浓厚的兴趣。在这篇综述中，我们总结了 RecQ 解旋酶结构和机制研究的最新进展，并讨论了它们在各种 DNA 修复途径中的作用。最后，我们考虑了利用 RecQ 解旋酶作为治疗靶点的潜力，并回顾了近年来针对 RecQ 解旋酶作为癌症治疗药物的小分子的开发进展。
