通过两种不同的机制修复来自酒精的DNA交叉链接
Michael R Hodskinson1, Alice Bolner2, Koichi Sato2
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|March 6, 2020
概括
酒精代谢物乙会导致DNA损伤. 修复这些DNA交叉链路有两种途径:Fanconi贫血 (FA) 途径和涉及DNA聚合酶REV1的新型切除独立机制,显示出不同的修复结果.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 乙化物是一种反应性酒精代谢物,会损害DNA,并与酒精相关的癌症有关.
- 乙化解毒和DNA修复途径受损,如Fanconi贫血 (FA),增加癌症风险和血液干细胞消耗.
- 乙诱导的DNA损伤的确切性质及其修复机制在很大程度上是未知的.
研究的目的:
- 调查乙引起的DNA损伤,并阐明其修复机制.
- 描述涉及维修乙诱导的DNA跨链路的途径.
主要方法:
- 在Xenopus蛋提取物中产生乙甲诱导的DNA链交联.
- 分析DNA修复途径,包括Fanconi贫血 (FA) 途径和复制分叉融合.
- 确定参与修复过程的关键酶和DNA聚合酶,如REV1.
主要成果:
- 确定了两种复制合的途径来修复乙诱导的DNA跨链.
- 该途径修复这些交叉链路类似于西斯,但突变频率增加和变化的频谱.
- 发现了第二条涉及复制分叉融合和交叉链本身的途径,由REV1完成,从而产生了独特的突变频谱.
结论:
- 这项研究确定了由内源性酒精代谢物乙引起的DNA链间交叉连接的修复途径.
- 已经确定了这些交叉链路的切除独立的修复机制.
- 这些发现突出了与不同DNA交联修复途径相关的独特修复结果和突变特征.
相关概念视频
Fixing Double-strand Breaks
14.1K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
14.1K
Fixing Double-strand Breaks
4.1K
4.1K
Overview of DNA Repair
33.2K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
33.2K
Overview of DNA Repair
9.4K
9.4K
Homologous Recombination
62.0K
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...
62.0K
Nucleotide Excision Repair
40.4K
Overview
40.4K


