核酸切除DNA修复与与年龄相关的血管功能障碍有关
Matej Durik1, Maryam Kavousi, Ingrid van der Pluijm
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, Netherlands.
Circulation
|June 19, 2012
概括
基因组不稳定性加速与年龄相关的血管功能障碍和硬. 修复DNA基因变异与动脉硬有关,支持基因组不稳定性.
科学领域:
- 基因组学就是基因组学.
- 血管生物学 血管生物学
- 衰老研究研究 衰老研究
背景情况:
- 在衰老,动脉样硬化和糖尿病中,血管功能障碍与DNA损伤和细胞衰老有关.
- 假设在衰老过程中累积的DNA损伤有助于血管功能障碍.
研究的目的:
- 调查基因组不稳定性在年龄相关血管功能障碍中的作用.
- 探索DNA修复基因变异与人类血管硬之间的关联.
主要方法:
- 利用具有缺陷核酸切除修复基因 (Ercc1和Xpd) 的小鼠来建模基因组不稳定性.
- 在这些小鼠中评估了年龄相关的血管功能,包括血管扩展功能和硬度.
- 在AortaGen联盟中分析了DNA修复基因中的单核酸多态性和动脉硬性之间的关联.
主要成果:
- 具有基因组不稳定的小鼠表现出加速的血管细胞衰老,血管扩展器功能障碍,血管硬性增加和血压升高.
- 内皮氧化合成酶水平和光滑肌肉细胞功能与血管扩张器功能障碍有关.
- 在人类中发现了DDB2基因单核酸多态性和动脉-股骨脉动波速之间存在显著的关联.
结论:
- 基因组不稳定性重复并加速年龄相关的血管功能障碍,反映了人类的状况.
- 人类DNA修复基因的变异与血管硬的标志物有关.
- 这项研究支持基因组不稳定性对心血管疾病发展的重大贡献.
相关概念视频
01:08Nucleotide Excision Repair
Overview
02:25Overview of DNA Repair
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...
01:54Base Excision Repair
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...
01:08Nucleotide Excision Repair
Overview
01:54Base Excision Repair
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...
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...