在Saccharomyces cerevisiae Rad51和Dmc1核蛋白丝中,由ATP水解驱动的结构转变
Yeonoh Shin1, Stefan Y Kim1, Eric C Greene1
1Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, New York, New York, USA.
The Journal of biological chemistry
|July 28, 2025
概括
对DNA修复蛋白Rad51和Dmc1的结构洞察力揭示了ATP水解如何驱动必要的DNA修复丝的分解,保持基因组稳定性和遗传多样性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 同源重组 (HR) 对基因组稳定性和遗传多样性至关重要.
- Rad51和Dmc1是关键的ATP依赖的DNA重组酶,形成HR的核蛋白丝.
- 导线稳定性由ATP结合和水解调节,影响HR过程.
研究的目的:
- 阐明了Rad51/Dmc1发光线动态的基础结构机制.
- 为了将ADP结合结构与先前确定的ATP结合状态进行比较.
- 提出一种与ATP水解相关的导线拆卸模型.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定结构.
- 研究了Saccharomyces cerevisiae Rad51和Dmc1重组酶的研究结果.
- 进行了ADP结合和ATP结合纤维的结构比较.
主要成果:
- 获得了ADP结合的Rad51和Dmc1纤维的冷EM结构.
- 确定了ATP和ADP结合状态之间的详细结构差异.
- 我们了解了ATP水解过程中的形状变化.
结论:
- 在Rad51/Dmc1细分线中,ATP的水解到ADP会诱导Rad51/Dmc1细分线中的结构转变.
- 这些转换的目的是为了促进核蛋白丝的分解.
- 这些发现为调节HR路径进展提供了一个新的模型.
相关概念视频
Restarting Stalled Replication Forks
5.9K
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,...
5.9K
Generation of Straight or Branched Actin Filaments
3.0K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.0K
DNA Damage can Stall the Cell Cycle
9.3K
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...
9.3K
Adaptability of Cytoskeletal Filaments
3.9K
The cytoskeleton is a complex dynamic structure performing varied functions based on cellular requirements. The adaptability of the individual filaments in the cytoskeleton determines their ability to perform various functions within the cell. It can undergo rapid reorganization during processes like cell division or remain stable for several hours as in the interphase. The adaptability of these filaments depends on stringent regulatory mechanisms. The microfilament and microtubules of the...
3.9K
Disassembly of Intermediate Filaments
2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
Actin Filament Depolymerization
3.2K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.2K


