通过核细胞核粒子中C4'-氧化基基位的快速裂变来进行质子修饰
Chuanzheng Zhou1, Jonathan T Sczepanski, Marc M Greenberg
1Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Journal of the American Chemical Society
|March 28, 2013
概括
氧化剂会造成DNA损伤,形成氧化基底部部位. 基因组加速DNA链分裂,并将这种损伤转移到自身,可能会影响基因调节.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- C4'-氧化基底部部位是由氧化剂,包括细胞毒性抗瘤药物产生的DNA损伤.
- 这种损伤具有性不稳定性,可以导致DNA链分裂.
- 了解DNA损伤和修复机制对于癌症治疗和理解基因调节至关重要.
研究的目的:
- 研究核素核粒体内C4'-氧化基底部位的形成和处理中组织蛋白质的作用.
- 为了阐明DNA链分裂和DNA-蛋白质交叉链接在这个损伤的机制.
- 为了确定氧化基底部部位的命运,其与组织蛋白的相互作用后.
主要方法:
- 在核细胞核粒子内的定义位置生成C4'-氧化基位.
- 分析DNA链裂变率在存在或缺少基因组蛋白的情况下.
- 描述DNA-蛋白质交叉链接和氧化基底部部位转移到基因组蛋白的特征.
主要成果:
- 希斯蛋白显著增加C4'-氧化基底部部位的DNA链分裂 (130-550倍).
- 链分裂通过希夫基中间体发生,但DNA-蛋白质交叉链是不稳定的.
- 氧化基底部部位被完全从DNA中移除,并转移到靠近基因组蛋白的氨酸丰富的尾部区域,作为乳.
- 这种修改分布在基因素的氨基末尾中的几个残留物中.
结论:
- 基因组蛋白在处理C4'-氧化基底位点方面发挥着关键作用,加速DNA链分裂.
- 将DNA损伤转移到组织素是DNA损伤处理的新途径.
- 这种DNA损伤转移到组织蛋白可能会对基因调节和细胞对氧化应激反应产生影响.
相关概念视频
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
02:10The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...