基因配对的高保真性由DNA中的2-selenothymidine在DNA中的基础配对
Abdalla E A Hassan1, Jia Sheng, Wen Zhang
1Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA.
Journal of the American Chemical Society
|January 30, 2010
概括
研究人员合成了一种新的2-Se-thymidine衍生物来增强DNA基对特异性. 这种修改显著改善了对像T/G这样的摇摆基对的歧视,同时保留了正常的T/A配对,提高了DNA复制忠实度.
科学领域:
- 化学生物学 化学生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 基因配对对DNA的功能至关重要,包括遗传信息存储和复制忠诚度.
- 波动基配对 (例如,T/G) 降低了特异性并损害了DNA聚合酶的准确性.
- 了解和增强基对特异性是准确核酸过程的关键.
研究的目的:
- 开发一种化学策略,以提高DNA中的基对特异性.
- 为了调查动歧视中蒂米丁2位的固态和电子效应的作用.
- 合成和描述一种新的2-Se-thymidine衍生物,并将其纳入DNA.
主要方法:
- 合成2-Se-胺酸胺酸和Se-DNAs.
- 改造DNA的生物物理和结构研究.
- 原子探测使用在thymidine的2-位置.
主要成果:
- 新型的2-Se-thymidine ((Se) T) 衍生物已成功合成并纳入DNA (Se-DNAs).
- 重的2-Se原子显著增加了对T/G波动和T/C不匹配的基对的歧视.
- (Se) T/A基对的稳定性与原生T/A基对相比,表明保留了沃森-克里克配对.
结论:
- 2-Se替代提供了一种独特的化学策略,通过操纵固态和电子性质来增强基对特异性.
- 这种修改为研究特定基对识别提供了一个潜在的工具,这对于复制,转录和翻译忠实性至关重要.
- 原子替代对于核酸结构和功能研究,包括X射线晶体学,是有价值的.
相关概念视频
02:27DNA Base Pairing
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
02:27DNA Base Pairing
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
01:31Proofreading
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Errors During Replication are Corrected by the DNA Polymerase Enzyme
01:43Proofreading
Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA strand. DNA polymerase has a higher affinity for the correct base to ensure fidelity in DNA replication. The DNA polymerase furthermore proofreads during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.Errors during Replication Are Corrected by the DNA Polymerase EnzymeGenomic DNA is synthesized in...
02:27Base-pairing and DNA Repair
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...