通过Spo11的协同切割揭示了介质DNA断裂机制
Dominic Johnson1, Margaret Crawford1, Tim Cooper1
1Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
Nature
|June 10, 2021
概括
研究人员发现,Spo11蛋白在半变化过程中会产生多个DNA双链断裂 (DSB),形成DNA间隙. 这一发现修改了我们对介质重组和缺口修复机制的理解.
科学领域:
- 分子生物学
- 遗传学
- 细胞生物学
背景情况:
- 介质变异期间的遗传重组对于精确的染色体分离至关重要.
- 由土酶样蛋白Spo11启动的DNA双链断裂 (DSB) 是介质重组的关键中间体.
- 目前尚不清楚Spo11催化DNA裂变及其基质结合的确切机制.
研究的目的:
- 调查Spo11介导的 DNA 双链断裂 (DSB) 形成的详细机制.
- 描述除单个切割之外的DSB形成的新模式.
- 阐明这些发现对 meiotic 重组和 DNA 修复的含义.
主要方法:
- 用了Saccharomyces cerevisiae作为一个模型生物.
- 采用介质后代的深度测序来分析重组事件.
- 使用Spo11核心复合体进行了体外DNA结合测试.
主要成果:
- 确定了由33到100多个基对隔开的"双切片"的形成.
- 观察到这些双切片的长度在酵母和小鼠中保持10.5个基对的周期性.
- 提供了支持相邻的Spo11分子与DNA螺旋相对固定方向的模型的证据.
- 检测到与Spo11产生的DNA缺口相一致的重组痕.
结论:
- Spo11可以产生相邻的DSB,在半球变化过程中产生DNA缺口.
- 双切长度的周期性表明Spo11在DNA上的方向受限.
- 这些发现扩大了弥合中缺口修复的概念,包括Spo11启动的DNA缺口,修改了当前的DSB形成机制模型.
相关概念视频
02:08Gene Conversion
10.2K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
10.2K
02:37Restarting Stalled Replication Forks
6.0K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.0K
02:31Homologous Recombination
57.7K
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...
57.7K
02:04Fixing Double-strand Breaks
13.3K
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...
13.3K
02:04Fixing Double-strand Breaks
3.7K
3.7K
02:57Meiosis vs. Mitosis
63.1K
Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
63.1K