在介质重组过程中,DNA损伤反应激酶Mec1ATR及其激活剂Rad24RAD17的可分离作用
Margaret R Crawford1,2, Jon A Harper1, Tim J Cooper1
1Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, United Kingdom.
PLoS genetics
|December 9, 2024
概括
介质变化过程中被编程的DNA断裂是由Mec1和Rad24调节的. 这些因素的丧失改变了重组和交叉分布,影响了全基因组的空间调节.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 介质形成涉及被Spo11.11启动的被编程的DNA双链断裂 (DSB).
- DNA损伤反应 (DDR) 激酶Mec1ATR和检查点加载器Rad24RAD17是由DSB激活的.
- 之前的研究在单个位置检查了Mec1和Rad24,但基因组在介质重组中的全基因组作用仍然不清楚.
研究的目的:
- 描述Mec1和Rad24在介质重组中的全基因组作用.
- 调查Mec1和Rad24如何影响DSB形成,重组结果和交叉 (CO) 分布.
- 了解介质重组的空间调节.
主要方法:
- 使用删除不匹配修复蛋白Msh2.
- 通过调节 Ndt80 转录因子来控制介质预相长度.
- 启用全基因组映射介质后代来分析重组模式.
主要成果:
- 删除RAD24,由缩短的预相,减少的重组频率和子活性的驱动.
- 丧失Mec1功能增加了重组频率,对子生存能力的影响较小.
- 缺少Rad24或Mec1导致更频繁的复杂多染色体事件和随机CO分布,表明空间调节受损.
结论:
- Mec1和Rad24在交叉 (CO) 调节中共享角色,它们的损失减少了全球干扰.
- Rad24充当了亲交叉因子,而Mec1调节了重组频率.
- 丢失Mec1可以抑制更广泛的CO调节缺陷,这些缺陷是由DNA损伤反应的废除引起的.
相关概念视频
02:37Restarting Stalled Replication Forks
5.7K
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,...
5.7K
02:31Homologous Recombination
50.2K
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...
50.2K
02:37DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
01:30Crossing Over
4.2K
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
4.2K
02:04Fixing Double-strand Breaks
12.3K
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...
12.3K
02:15M-Cdk Drives Transition Into Mitosis
5.5K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K