在不匹配的DNA中,脊柱形态平衡与酶活性相关
M N Westwood1, A Pilarski2, C Johnson2
1Biophysics Program, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.
Biochemistry
|September 12, 2023
概括
DNA修复酶使用酸盐骨干平衡来识别不匹配. 这项研究将DNA骨干能量与酶动力学联系起来,揭示了DNA修复和核酸审讯中的关键机制.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 在DNA中T:G不匹配主要是由甲基化CpG去胺或不正确的核酸结合引起的.
- 通过DNA修复酶识别这些不匹配的机制尚未完全理解.
- 蛋白质-DNA骨干相互作用被假设在不匹配识别和修复中起着至关重要的作用.
研究的目的:
- 为了调查DNA酸盐骨干能量学在不匹配识别中的作用.
- 为了将DNA骨干平衡与各种DNA修复酶的基质依赖性相关联.
- 阐明在修复过程中促进蛋白质-DNA相互作用的构造性质.
主要方法:
- 利用31P核磁共振 (NMR) 光谱来研究DNA骨干BI-BII相互转换的能量.
- 在正规DNA,不匹配DNA和具有病变的DNA之间比较能量差异 (ΔG).
- 相关的DNA酸盐骨干平衡 (Keq) 与酶动力学和胺DNA糖酶 (TDG),MBD4和其他酶的结合参数.
主要成果:
- 之前发现了与正规DNA相比,修改DNA中脊柱互转换的ΔG (1-2 kcal/mol) 的阶段性差异.
- 在DNA酸盐骨干平衡 (Keq) 和测试酶的动力学/结合参数之间建立了强烈的相关性.
- 在这些相关性中证明了序列和基对依赖性.
结论:
- DNA酸盐骨干平衡与关键DNA修复酶的基质依赖关系密切相关.
- 这种脊柱平衡可能在不匹配的识别中起着重要作用.
- 在酶询问过程中,如核酸翻转等,形态重组和能量受脊柱性质的影响.
相关概念视频
01:20Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
02:02DNA Topoisomerases
31.4K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.4K
02:31Homologous Recombination
50.6K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.6K
02:05DNA as a Genetic Template
22.0K
Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
22.0K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
00:55DNA Helicases
21.4K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.4K