通过不同的机制,招募Mec1和Ddc1检查点蛋白质到双链断裂
1Division of Biological Science, Graduate School of Science, Nagoya University, CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-0814, Japan.
概括
DNA 损伤会触发细胞循环停止和DNA 修复基因表达. 在酵母中,Mec1和Ddc1蛋白独立地识别了DNA损伤部位,这表明了不同的损伤识别途径.
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:
- 细胞在DNA损伤时激活检查点路径,以阻止细胞周期的进展并启动DNA修复.
- 发芽酵母中的同质切换 (HO) 内核酶在交配类型 (MAT) 位点诱导特定的双链断裂,作为DNA损伤研究的模型.
研究的目的:
- 调查关键检查点蛋白Mec1和Ddc1对由HO内核酶诱导的DNA损伤部位的招募机制.
- 为了确定Mec1,Ddc1,Rad9和Rad24在DNA损伤识别过程中的相互依赖.
主要方法:
- 利用染色体免疫沉 (ChIP) 实验来检测与MAT位置的蛋白质关联.
- 表达的HO内核酶诱导特定位点的DNA双链断裂.
- 分析了Ddc1和Mec1招募对其他检查点蛋白质 (Rad24,Mec1,Rad9) 的依赖性.
主要成果:
- 发现Ddc1蛋白与HO表达后的MAT位点区域结合,这一过程依赖Rad24,但不依赖Mec1或Rad9.
- Mec1蛋白也与DNA分裂部位区域独立于Ddc1,Rad9和Rad24相关.
- 这些发现表明Mec1和Ddc1在DNA损伤部位的独立招募.
结论:
- Mec1和Ddc1通过不同的途径被招募到DNA损伤部位.
- 这项研究表明,在真核细胞中,至少存在两个不同的机制来识别DNA损伤.
相关概念视频
Mismatch 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...
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...


