内源性化物诱导的DNA-蛋白质交叉链接通过转录合修复解决
Yasuyoshi Oka1,2, Yuka Nakazawa1,2, Mayuko Shimada1,2
1Department of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, Japan.
Nature cell biology
|April 10, 2024
概括
通过转录合修复 (TCR) 和化物清除,DNA-蛋白质交叉链 (DPC) 得到解决. 这一过程对于预防基因组不稳定性和理解像AMED综合征这样的前列腺综合征至关重要.
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:
- 来自基的DNA-蛋白质交叉链 (DPC) 阻碍了DNA复制和转录.
- 在DPC修复和化物清除中的缺陷会导致前列腺综合征 (例如,Ruijs-Aalfs综合征,AMED综合征).
- 在转录过程中解决DPC的机制尚不清楚.
研究的目的:
- 研究细胞如何解决转录过程中产生的DPC.
- 确定参与转录合DPC修复 (TC-DPCR) 的分子参与者.
- 阐明TC-DPCR和化物清除在预防基因毒性的作用.
主要方法:
- 开发了一种高通量测序技术 (DPC-seq),用于全基因组的DPC映射.
- 利用蛋白质组学来识别与DPC相互作用的蛋白质.
- 采用了一种缺少化物清除和TCR的小鼠模型.
主要成果:
- 化物诱导的DPCs通过转录合修复 (TCR) 得到有效的解决.
- TCR复合体,VCP/p97和蛋白酶体对于去除甲诱导的DPCs至关重要.
- 通过TFIIS介导的RNAPII转录的切割减轻了转录障碍.
- 一个小鼠模型显示,当化物清除和TCR受损时,DPC在活跃转录的区域积累.
结论:
- 转录合DPC修复 (TC-DPCR) 是在转录期间解决DPC的关键途径.
- TC-DPCR和化物清除对于对代谢性基因毒素的保护至关重要.
- 这些发现解释了AMED综合征和其他TCR相关疾病的分子基础.
更多相关视频
11:58A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells
Published on: March 5, 2018
8.3K
07:55Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
Published on: September 11, 2022
1.8K
相关概念视频
02:31Homologous Recombination
50.5K
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...
50.5K
01:08Nucleotide Excision Repair
37.0K
Overview
37.0K
02:25Overview of DNA Repair
31.0K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.0K
01:36Mismatch Repair
40.1K
Overview
40.1K
01:54Base Excision Repair
22.3K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.3K
02:04Fixing Double-strand Breaks
12.6K
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...
12.6K