遗传 ›› 2022, Vol. 44 ›› Issue (6): 466-477.doi: 10.16288/j.yczz.22-067

• 综述 • 上一篇    下一篇

DNA氧化损伤8-羟鸟嘌呤与肿瘤的发生发展

赵岩1, 王晨鑫2(), 杨天明2, 李春爽2, 张丽宏2, 杜冬妮2, 王若曦3, 王静4, 魏民2, 巴雪青2()   

  1. 1. 吉林省疾病预防控制中心媒介生物防治科,长春 130062
    2. 东北师范大学生命科学学院分子表观遗传学教育部重点实验室,长春 130024
    3. 山东师范大学生命科学学院,济南 250014
    4. 吉林大学中日联谊医院呼吸科,长春 130061
  • 收稿日期:2022-03-10 修回日期:2022-04-16 出版日期:2022-06-20 发布日期:2022-04-22
  • 通讯作者: 巴雪青 E-mail:wangcx968@nenu.edu.cn;baxq755@nenu.edu.cn
  • 作者简介:赵岩,学士,副主任技师,研究方向:细胞生物学。E-mail: shaunna68@sina.com
  • 基金资助:
    国家自然科学基金项目和吉林省自然科学基金资助(31900557);国家自然科学基金项目和吉林省自然科学基金资助(32170591);国家自然科学基金项目和吉林省自然科学基金资助(Nos.31970686);国家自然科学基金项目和吉林省自然科学基金资助(No. 20210101356JC)

Linking oxidative DNA lesion 8-OxoG to tumor development and progression

Zhao Yan1, Wang Chenxin2(), Yang Tianming2, Li Chunshuang2, Zhang Lihong2, Du Dongni2, Wang Ruoxi3, Wang Jing4, Wei Min2, Ba Xueqing2()   

  1. 1. Department of Biological Vector Control, Center for Disease Control and Prevention of Jilin Province, Changchun 130062, China
    2. The Key Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal University, Changchun 130024, China
    3. College of Life Sciences, Shandong Normal University, Jinan 250014, China
    4. Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun 130061, China
  • Received:2022-03-10 Revised:2022-04-16 Online:2022-06-20 Published:2022-04-22
  • Contact: Ba Xueqing E-mail:wangcx968@nenu.edu.cn;baxq755@nenu.edu.cn
  • Supported by:
    Nos.Supported by the National Natural Science Foundation of China(31900557);Nos.FSupported by the National Natural Science Foundation of China(32170591);Nos.Supported by the National Natural Science Foundation of China(Nos.31970686);the Natural Science Foundation of Jilin Province of China(No. 20210101356JC)

摘要:

有氧代谢有机体细胞无法避免活性氧(reactive oxygen species, ROS)的伤害。ROS会造成多种形式的DNA损伤,其中鸟嘌呤G的氧化产物8-羟鸟嘌呤(8-oxoG)是频度最高的一种DNA氧化损伤,由特异性的糖苷酶OGG1识别并开启碱基切除修复通路完成修复。8-oxoG如果没有及时修复,可能会在复制的过程中引入G:C配对到T:A配对的碱基颠换突变。因此8-oxoG的积累或OGG1修复功能异常被认为会影响基因功能,进而导致肿瘤或衰老相关疾病的发生,然而直接实验证据却极为有限。近年来一系列研究表明,8-oxoG倾向于产生在基因的调控区,在这种情形下,8-oxoG可视为一种表观遗传学修饰,而OGG1则是这一信息的特异性读取者,OGG1对底物的识别、结合或切除会引发DNA构象或组蛋白修饰的改变,进而引起基因表达的上调或下调。因此,除了潜在的遗传毒性,鸟嘌呤氧化损伤与肿瘤的关联与其通过表观遗传学机制引发基因表达的异常密切相关。本文对8-oxoG及修复酶OGG1与肿瘤发生发展的关联机制进行了分析与总结,旨在提示研究人员从新的视角解读DNA氧化损伤与肿瘤的关系,并为肿瘤的治疗提供新的思路和靶点。

关键词: 8-羟鸟嘌呤, 8-羟鸟嘌呤DNA糖苷酶1, 表观遗传调控, 基因表达, 肿瘤

Abstract:

Cells of the aerobic metabolic organism are inevitably subjected to the damage from reactive oxygen species (ROS). ROS cause multiple forms of DNA damage, among which the oxidation product of guanine G 8-hydroxyguanine (8-oxoG) is the most frequent DNA oxidative damage, recognized by the specific glycosidase OGG1 that initiates the base excision repair pathway. If left unrepaired, 8-oxoG may pair with A instead of C, leading to a mutation of G: C to T: A during replication. Thus, the accumulation of 8-oxoG or the abnormal OGG1 repair is thought to affect gene function, which in turn leads to the development of tumor or aging-related diseases. However, a series of recent studies have shown that 8-oxoG tends to be produced in regulatory regions of the genome. 8-oxoG can be regarded as an epigenetic modification, while OGG1 is a specific reader of this information. Substrate recognition, binding or resection by OGG1 can cause DNA conformation changes or affect histone modifications, causing up-regulation or down-regulation of genes with different properties. Thus, in addition to the potential genotoxicity, the association of guanine oxidative damage with development of tumors is closely related to its aberrant initiation of gene expression through epigenetic mechanisms. In this review, we summarize the underlying mechanism of 8-oxoG and repair enzyme OGG1 in tumor development and progression, with aims to interpret the relationship between DNA oxidative damage and tumor from a new perspective, and provide new ideas and targets for tumor treatment.

Key words: 8-oxoG, OGG1, epigenetic regulation, gene expression, tumor