Base excision repair and design of small molecule inhibitors of human DNA polymerase β.

Base excision repair and design of small molecule inhibitors of human DNA polymerase β.
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DOI:
10.1007/s00018-010-0489-1
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发表时间:
2010-11
影响因子:
8
通讯作者:
Heacock, Michelle L.
Heacock, Michelle L.
中科院分区:
生物学1区
文献类型:
--
作者:
Wilson, Samuel H.;Beard, William A.;Shock, David D.;Batra, Vinod K.;Cavanaugh, Nisha A.;Prasad, Rajendra;Hou, Esther W.;Liu, Yuan;Asagoshi, Kenjiro;Horton, Julie K.;Stefanick, Donna F.;Kedar, Padmini S.;Carrozza, Michael J.;Masaoka, Aya;Heacock, Michelle L.

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碱基切除修复(BER)可以在内源性或外源性遗传毒性应激后保护细胞,BER的缺乏可以使细胞对应激诱导的细胞凋亡和坏死细胞死亡、突变和染色体重排高度敏感。然而,对哺乳动物BER系统的理解还不完全,因为它非常复杂,并且有许多备份过程可以补充任何一个步骤中的不足。由于缺乏信息,我们无法准确预测针对BER的治疗方法。对BER的深入了解最终将使我们能够进行更有意义的临床干预。在这篇综述中,我们将涵盖哺乳动物BER和DNA聚合酶β的历史和最新信息,并讨论开发和使用小分子抑制剂来操纵BER的方法。在向其他人道歉的同时,我们将强调在我们实验室和我们合作者的实验室中获得的结果。
Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase β and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.
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