在分子拥挤条件下,长端粒DNA的串珠结构
Haiqing Yu1, Xiaobo Gu, Shu-ichi Nakano
1FIBER (Frontier Institute for Biomolecular Engineering Research), Konan University, 7-1-20 Minatijima-Minatomachi, Chuo-ku, Kobe 650-0047, Japan.
Journal of the American Chemical Society
|September 1, 2012
概括
长端粒DNA形成G-四重复结构. 分子拥挤增强了稳定性,但这种效应在较长的DNA中减弱,这表明端粒生物学中的复杂稳定性影响.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 端粒保护染色体末端,但它们的结构和稳定性是复杂的.
- 长端粒DNA序列,特别是 (T) 是对端粒功能至关重要的.
- 了解端粒中的G-四倍体形成对于理解基因组稳定性至关重要.
研究的目的:
- 在不同条件下研究长端粒DNA的结构和稳定性.
- 探索分子拥挤和离子存在 (Na+,K+) 对G-四重复形成的影响.
- 阐明DNA链接器在长端粒结构的整体稳定性中的作用.
主要方法:
- 在稀释和分子拥挤条件下研究了长端粒DNA ((T(2) AG(3)) ((n),n=4-20).
- 利用Na+和K+离子分析结构和热力学特性.
- 进行了水化研究,以了解G-四重复结构中的水相互作用.
主要成果:
- 长端粒DNA始终形成了分子内G-四复合体.
- Na+诱导了反平行G-四重复,而K+诱导了在拥挤下从混合结构转变为平行结构.
- 分子拥挤增加了G-四重复的稳定性,但这种效应随着DNA长度的增加而减弱.
结论:
- 长端粒DNA中的G-四倍体稳定性受分子拥挤和DNA长度的影响.
- G-四重复单元之间的链接区域看起来是有序的,而不是随机的线圈,影响了整体稳定性.
- 结果提供了对端粒生物学和药物设计的潜在目标的见解.
相关概念视频
01:32Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
02:21Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
02:41Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
00:58DNA Packaging
Overview
00:58Genomic DNA in Eukaryotes
Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
02:33The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...