仿真病毒基切割修复途径的生物化学重建
Shailesh B Lad1, Monica Upadhyay2, Pracheta Thorat3
1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, Maharashtra, India. Electronic address: https://twitter.com/shailesh2603.
Journal of molecular biology
|June 28, 2023
概括
咪米病毒病毒包装DNA基切除修复 (BER) 蛋白质,包括一种新型的 uracil-DNA糖核酶,AP-内核酶和聚合酶X. 这些酶在体外共同作用,修复含有 uracil 的 DNA,这表明它们在早期病毒感染中起作用.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 核细胞质大型DNA病毒 (NCLDVs) 拥有DNA复制和修复的基因,挑战了传统的病毒仅仅是寄生虫的观点.
- 病毒颗粒中的DNA修复酶的存在和功能尚未得到充分理解.
研究的目的:
- 研究NCLDV病毒中DNA基切除修复 (BER) 途径蛋白的包装和功能,特别是Mimivirus.
- 描述米米病毒中关键BER蛋白的酶活性,并评估它们的协作功能.
主要方法:
- 来自米米病毒和相关NCLDVs的病毒颗粒的蛋白质组学分析.
- 净化复合Mimivirus uracil-DNA glycosylase (mvUDG),AP-endonuclease (mvAPE) 和聚合酶X (mvPolX) 的生化特征.
- 在体外溶解试验用纯化的Mimivirus酶来评估BER通路功能.
主要成果:
- 蛋白质组学揭示了Mimivirus病毒中存在BER蛋白质的存在,但在马赛病毒或库拉病毒中没有.
- 发现米米病毒 uracil-DNA glycosylase (mvUDG) 可以从单链和双链DNA中切除 uracil.
- 咪咪病毒AP-内核酶 (mvAPE) 和聚合酶X (mvPolX) 分别表现出特定的DNA裂变和填空活动.
- 试管复制表明mvUDG,mvAPE和mvPolX通过长补丁BER连贯地修复含有 uracil 的DNA.
结论:
- 仿真病毒病毒包装功能性DNA基切除修复酶.
- 这些酶,特别是mvUDG,mvAPE和mvPolX,可以在体外合作修复含 uracil 的DNA.
- 包装的BER机器可能在米米病毒感染的早期阶段发挥作用,可能有助于宿主DNA修复或病毒基因组维护.
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