来自病毒基因组的非正规核酸干扰了氧化DNA损伤修复系统
Anna V Yudkina1, Anton V Endutkin2, Evgeniia A Diatlova2
1SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., Novosibirsk 630090, Russia; Novosibirsk State University, 2 Pirogova St., Novosibirsk 630090, Russia.
当细菌体使用Z核酸而不是腺因时,氧化DNA损伤控制会发生变化. 这种放松的控制可能会增加这些替代遗传系统中的突变发生.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 氧化损伤,特别是8-oxoguanine (8-oxoG),对有氧生物的基因组稳定性构成威胁.
- 一个专门的DNA修复系统 (GO系统) 通常可以防止由8-oxoG:腺素 (A) 错配引起的突变.
- 一些病毒利用非正规核酸,比如Z核酸 (2,6-二氨基酸) 取代A,导致尚未探索的基因组维护机制.
研究的目的:
- 为了研究GO系统酶如何在Z核酸的存在下处理氧化DNA损伤.
- 为了确定DNA修复酶的特异性是否受到Z替换A的影响.
主要方法:
- 评估了对抗8-oxoG和Z的修饰核酸的DNA聚合酶结合.
- 检查了 8-oxoG:Z 误对上 8-oxoguanine-DNA 糖酶 (Fpg) 的活性.
- 研究了不同细菌物种中Z:8-oxoG不匹配的腺因-DNA糖解酶 (MutY) 的活性.
主要成果:
- DNA聚合酶内含改性核酸 (dZMP与8-oxoG相对,8-oxodGMP与Z相对).
- Fpg显示没有从8-oxoG:Z不匹配中去除8-oxoG,类似于它对8-oxoG:A.的歧视.
- 与8-oxoG:A不匹配相比,MutY对Z:8-oxoG不匹配的活性显著降低.
- 这些偏好在Escherichia coli, Staphylococcus aureus和Lactococcus lactis的Fpg和MutY中是一致的.
结论:
- Z核酸的存在放松了GO系统酶的特异性,特别是MutY.
- 在含有Z的基因组中,这种受损的DNA修复可能导致突变发生的增加.
- 这一发现对理解基因组进化和具有替代遗传化学的生物体的稳定性有意义.
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