胺DNA糖酶对于通过链接的去胺基切除修复来进行活性DNA脱甲基化是必不可少的
Salvatore Cortellino1, Jinfei Xu, Mara Sannai
1Cancer Biology Program and Epigenetics and Progenitor Cells Keystone Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Cell
|July 5, 2011
概括
基因修复酶丁胺DNA糖酶 (TDG) 对于保护哺乳动物基因组免受过度DNA甲基化和积极去甲基化关键调节区域至关重要. 它的缺失导致胚胎死亡,揭示了它在表观遗传调节中的重要作用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 基因甲基化是基因沉默的关键表观遗传机制.
- 保护哺乳动物基因组免受新甲基化和活性脱甲基化的机制尚不完全理解.
研究的目的:
- 研究胺DNA糖酶 (TDG) 在DNA甲基化和脱甲基化中的作用.
- 阐明TDG在哺乳动物发育过程中的表观遗传调节中的功能.
主要方法:
- 在小鼠中,基因淘汰和TDG的催化失活.
- 对TDG与其他蛋白质相互作用的分析 (AID,GADD45a).
- 评估TDG在促进者招募 (p300) 和表观遗传状态中的作用.
主要成果:
- 在小鼠中,TDG淘汰或失活导致胚胎致死性.
- TDG对于招募p300到网红酸调节的促进剂至关重要.
- TDG保护CpG群岛免受过甲基化,并促进受管制的促进剂和增强剂的活性去甲基化.
- TDG与AID和GADD45a相互作用,表明在脱甲基化途径中发挥作用.
结论:
- 在发育过程中,TDG在维持适当的表观遗传状态方面发挥着双重作用.
- 提出了一种两步的DNA脱甲基化机制,涉及AID介导的脱胺,其次是TDG介导的切除修复.
相关概念视频
Base 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...
Base 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...
Overview 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...
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Overview 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...
Nucleotide Excision Repair
Overview
Nucleotide 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...


