人源核酸烷基化损伤修复酶ALKBH3在肿瘤进展和治疗中的作用

doi:10.3969/j.issn.1674-8115.2021.05.021

摘要/Abstract

摘要：

人源核酸烷基化损伤修复酶ALKBH3（alpha-ketoglutarate-dependent dioxygenase homolog 3）隶属于亚铁（Fe²⁺）和α-酮戊二酸（α-ketoglutarate，α-KG）依赖型双加氧酶AlkB家族。尽管ALKBH3具有与该家族其他同源蛋白成员高度类似的保守氨基酸序列和三级结构，但是ALKBH3对单链DNA或RNA上的N¹-甲基腺嘌呤和N³-甲基胞嘧啶等烷基化损伤具有独特的识别和去除功能。它的表达异常或功能异常与多种癌症的发生发展有紧密联系，被认为是抗肿瘤的潜在药物靶标。对于ALKBH3结构功能和调控机制的深入研究，将有助于进一步了解人体烷基化损伤修复过程中的分子机制，为研发靶向ALKBH3的抗肿瘤药物奠定基础。

关键词: 人源核酸烷基化损伤修复酶, ALKBH3, DNA烷基化损伤修复, 癌症

Abstract:

Human nucleic acid alkylation damage repair enzyme ALKBH3 (alpha-ketoglutarate-dependent dioxygenase homolog 3) belongs to Fe²⁺/α-Ketoglutarate (α-KG)-dependent AlkB dioxygenase family, and shares a highly conserved catalytic domain through the entire family. ALKBH3 specifically recognizes N¹-methyl adenine and N³-methyl cytosine on single-stranded DNA or RNA, and catalyzes their methyl group removal for alkylation damage repair. Previous studies have shown that ALKBH3 is highly expressed in various solid tumors, and thereby it has been considered as a potential anti-tumor drug target. Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNA alkylation damage repair, and lay the foundation for the development of anti-tumor drugs targeting ALKBH3.

Key words: alpha-ketoglutarate-dependent dioxygenase homolog 3, ALKBH3, DNA alkylation damage repair, cancer

中图分类号:

胡静燕, 张琳, 张良. 人源核酸烷基化损伤修复酶ALKBH3在肿瘤进展和治疗中的作用[J]. 上海交通大学学报(医学版), 2021, 41(5): 684-689.

Jing-yan HU, Lin ZHANG, Liang ZHANG. Function of human nucleic acid alkylation damage repair enzyme ALKBH3 in cancer progression and oncotherapy[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 684-689.

图/表 1

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