隔离酶介导的凝聚蛋白在相间分裂是DNA修复所需的
Koji Nagao1, Yoh Adachi, Mitsuhiro Yanagida
1Department of Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
Nature
|August 27, 2004
概括
塞库林对于保持分离酶稳定性和在辐射后使DNA修复成为可能至关重要. 这项研究表明,securin-separase复合物通过分裂凝聚素来帮助DNA修复,特别是在DNA损伤的部位.
科学领域:
- 细胞生物学 细胞生物学
- 分子遗传学 分子遗传学
- DNA 修复机制的修复机制
背景情况:
- 姐妹染色体在异相期间通过分离酶的作用被分离出来,这种分离作用会分裂凝聚体.
- 塞库林抑制分离酶活性,并被降解以允许细胞循环的进展.
- 除了细胞循环调节外,securin在DNA修复中的作用尚未完全被理解.
研究的目的:
- 为了研究securin (Cut2) 在DNA修复途径中的功能.
- 确定securin-separase影响DNA损伤反应的机制.
- 探索凝聚素分裂和DNA修复之间的相互作用.
主要方法:
- 使用的裂变酵母突变物,包括cut2(EA2),chk1,rad13,rhp51和rad21.
- 进行了双重突变分析,以评估DNA修复中的遗传相互作用.
- 采用突变凝聚素和蛋白酶死分离酶的实验来研究切割依赖的功能.
主要成果:
- 塞库林对于分离稳定性和由紫外线,X射线和玛射线辐射引起的DNA损伤的有效修复至关重要.
- 切割2(EA2) 突变体在紫外线损伤修复中表现出缺陷,尽管正常的DNA损伤检查点激活.
- 有证据表明,securin-separase通过凝聚素裂变促进DNA修复,这一过程依赖于Rad3激酶.
结论:
- 赛库林分离酶复合体在DNA修复中起着至关重要的作用,独立于其在亚纳相中的作用.
- 通过securin-separase的凝聚素分裂是DNA修复的关键机制,可能通过在相间细胞中去除局部凝聚素.
- 这一发现扩大了已知的securin-separase系统的功能,包括相间DNA损伤反应.
相关概念视频
Nucleotide Excision Repair
Overview
Fixing Double-strand Breaks
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...
Homologous Recombination
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...
Restarting Stalled Replication Forks
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, a...
Single-Strand DNA Binding Proteins
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Fixing Double-strand Breaks
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...


