Focus on DNA Glycosylases-A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets.
Focus on DNA Glycosylases-A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets.
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DOI：
10.3390/ijms21239226
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发表时间：
2020-12-03
影响因子：
5.6
通讯作者：
Timmins J
中科院分区：
文献类型：
--
作者：
Hans F;Senarisoy M;Bhaskar Naidu C;Timmins J
癌症是导致死亡的第二大原因，全世界每年有数千万人被诊断患有癌症。大多数放疗和化疗的目的是消灭癌细胞，特别是通过对DNA造成严重损害。然而，这种损伤的有效修复代表了对最初有效的细胞毒性药物的抗性的共同机制。因此，开发针对DNA修复途径的新一代抗癌药物，特别是针对负责去除受损碱基的碱基切除修复（BER）途径的新一代抗癌药物越来越受到关注。BER途径是由一组称为DNA糖基化酶的酶启动的。与下游几种BER酶不同，DNA糖基酶迄今为止受到的关注很少，这些酶的特异性抑制剂的开发也很滞后。然而，DNA糖基酶的失调也被认为在许多癌症和疾病的不同阶段发挥核心作用，因此抑制DNA糖基酶现在被认为是消除癌细胞的有效策略。本文综述了DNA糖基酶在正常细胞和癌细胞中的活性、调控模式及其作为抗癌药物靶点的潜力。
Cancer is the second leading cause of death with tens of millions of people diagnosed with cancer every year around the world. Most radio- and chemotherapies aim to eliminate cancer cells, notably by causing severe damage to the DNA. However, efficient repair of such damage represents a common mechanism of resistance to initially effective cytotoxic agents. Thus, development of new generation anticancer drugs that target DNA repair pathways, and more particularly the base excision repair (BER) pathway that is responsible for removal of damaged bases, is of growing interest. The BER pathway is initiated by a set of enzymes known as DNA glycosylases. Unlike several downstream BER enzymes, DNA glycosylases have so far received little attention and the development of specific inhibitors of these enzymes has been lagging. Yet, dysregulation of DNA glycosylases is also known to play a central role in numerous cancers and at different stages of the disease, and thus inhibiting DNA glycosylases is now considered a valid strategy to eliminate cancer cells. This review provides a detailed overview of the activities of DNA glycosylases in normal and cancer cells, their modes of regulation, and their potential as anticancer drug targets.
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影响因子：
78.5
作者：
Chabner, BA;Roberts, TG
通讯作者：
Roberts, TG
影响因子：
3.8
作者：
Akbari M;Solvang-Garten K;Hanssen-Bauer A;Lieske NV;Pettersen HS;Pettersen GK;Wilson DM 3rd;Krokan HE;Otterlei M
通讯作者：
Otterlei M
影响因子：
14.9
作者：
Bauer NC;Corbett AH;Doetsch PW
通讯作者：
Doetsch PW
影响因子：
3.8
作者：
Chan MK;Ocampo-Hafalla MT;Vartanian V;Jaruga P;Kirkali G;Koenig KL;Brown S;Lloyd RS;Dizdaroglu M;Teebor GW
通讯作者：
Teebor GW
UNG2 脱乙酰化赋予癌细胞对过氧化氢诱导的细胞毒性的抵抗力。
影响因子：
7.4
作者：
Bao, Yantao;Tong, Lili;Zhu, Wei-Guo
通讯作者：
Zhu, Wei-Guo