在人体细胞中缺少主要AP内核酶,APE1的备份基底切割DNA修复
Daria V Kim1,2, Evgeniia A Diatlova1, Timofey D Zharkov1
1Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia.
International journal of molecular sciences
|January 11, 2024
概括
人类细胞拥有对阿普里尼克/阿普里米尼克 (AP) 位点的备份DNA修复通路,即使没有主要酶APE1. 这些途径,包括一个涉及NTHL1的途径,确保有效地修复DNA损伤.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- DNA 修复机制的修复机制
背景情况:
- 阿普里尼克/阿普里米尼克 (AP) 位点是DNA修复过程中至关重要的常见DNA病变.
- 人体细胞中AP位点修复的主要酶是AP内核酶1 (APE1).
- 在体内,其他AP位点修复途径在很大程度上仍然未被描述.
研究的目的:
- 研究缺少必需的AP内核酶APE1.1的人类细胞中AP位点修复机制.
- 识别潜在的备份路径用于AP站点修复.
- 阐明NTHL1在替代DNA修复中的作用.
主要方法:
- 使用的APEX1淘汰赛HEK293FT细胞.
- 在增强的绿色光蛋白基因中采用基于转录性突变发生的记者系统.
- 在具有或没有APE2的细胞和化学阻断的水解中评估了AP点修复.
主要成果:
- 缺少APEX1的细胞有效地修复了抗β消除的四二氨酸AP位点模拟物.
- 这种修复能力即使在APE2淘汰赛后也保持不变.
- 在APEX1无细胞中,当水解被阻止时,乌拉修复需要NTHL1,一种催化β消除的酶.
结论:
- 人类细胞至少有两个备份路径来修复AP位点.
- 一个已识别的备份路径依赖于酶NTHL1.1.
- 这些发现凸显了DNA修复系统在维护基因组完整性方面的强度.
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