基配对和复制性处理的形式amidopyrimidine-dG DNA 损伤
Matthias Ober1, Heiko Müller, Carsten Pieck
1Department of Chemistry and Biochemistry Ludwig-Maximilians-University Munich, D-81377 Munich, Germany.
Journal of the American Chemical Society
|December 22, 2005
概括
2'-脱氧氨酸 (FaPydG) 的DNA损伤 2,6-氨酸-4-氧-5-胺-5-胺-5-氨酸保留了关氨酸.
科学领域:
- 分子生物学分子生物学
- DNA损伤和修复的过程
- 生物化学 生物化学
背景情况:
- 氧化应激会诱导DNA损伤,包括主要损伤2,6-胺-4-氧-5-formamidopyrimidine的2 -deoxyguanosine (FaPydG).
- 了解FaPydG的基配对和编码潜力对于估计其突变效应至关重要.
研究的目的:
- 在DNA复合体内研究基于环丹的FaPydG (cFaPydG) 类比的基配对特性和热力学稳定性.
- 通过动态原料延伸研究来确定FaPydG病变的突变性潜力和复制忠实度.
主要方法:
- 合成含有cFaPydG的寡核酸,这是2 - 脱氧氨酸 (cdG) 的循环类型,以及8-oxo-7,8-dihydro-2 - 脱氧氨酸 (8-oxodG).
- 使用度依赖点测量 (van't Hoff图) 来确定双重热力学稳定性.
- 使用Saccharomyces cerevisiae Pol eta.进行动力原料扩展研究.
主要成果:
- cFaPydG损伤显著破坏了DNA复合体的稳定性,而细胞因子 (dC) 是最佳的基配对伙伴.
- 与8-oxodG不同的是,FaPydG无法与腺素 (dA) 形成稳定的基对.
- 动力学研究表明,cFaPydG被S. cerevisiae Pol eta无错复制,并有效地插入dC,表明保留了编码潜力.
结论:
- 尽管FaPydG损伤导致双重不稳定,但通过与细胞因子优先配对,仍然保留了关氨酸 (dG) 的编码潜力.
- 在cdG中的环丹替代对双重稳定性具有边际影响,而与正规脱氧氨 (dG) 相比.
- FaPydG代表了DNA损伤,可以准确地复制,可能减轻其突变性影响.
相关概念视频
Overview of DNA Repair
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The first step of...
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Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
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