转录错误的序列依赖的动态机制
Tripti Midha1, Anatoly B Kolomeisky1,2,3,4, Oleg A Igoshin1,2,5,6
1Center for Theoretical Biological Physics, Rice University, Houston, TX 77005.
概括
这项研究揭示了DNA序列上下文如何影响RNA聚合酶II的转录保真性. 了解这些依赖序列的错误率对于精确的基因表达和防止过早停止编码子等错误至关重要.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 遗传学 是一个遗传学.
背景情况:
- 转录忠实性对于准确的基因表达至关重要.
- 控制转录忠实性的机制,特别是序列依赖性,尚未完全理解.
- 之前的研究发现了基于核酸身份的错误率变化,但缺乏全面的显微镜解释.
研究的目的:
- 开发一个整合转录校对和DNA序列效应的理论模型.
- 在RNA聚合酶II转录过程中定量表征核酸特异性错误率.
- 为了阐明对依赖序列的转录忠实性的微观解释.
主要方法:
- 开发了一种结合校对机制和不均DNA序列效应的理论方法.
- 使用通过蒙特卡洛模拟验证的第一通道分析.
- 对现有数据集进行生物信息分析.
主要成果:
- 该模型准确地复制实验误差率,并预测运动参数.
- 核酸合并率遵循层次结构U
- 确定下游核酸在+1和+2位置显著影响错误率,而pyrimidines在+2减少错误,而+3位置没有影响.
- 由于依赖序列的错误率,在BRCA1基因中出现过早停止编码子错误的可能性增加.
结论:
- 在转录过程中,DNA序列上下文批判性地调节了核酸结合动力学.
- 这些发现促进了对转录忠实性及其功能后果的理解,包括对遗传疾病的影响.
- 该研究为预测和理解转录错误模式提供了定量框架.
相关概念视频
Genome Copying Errors
4.4K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.4K
Improving Translational Accuracy
11.8K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.8K
Coordination of Gene Expression Processes in Bacteria
143
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
143
Proofreading
6.6K
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...
Errors During Replication are Corrected by the DNA Polymerase...
6.6K
Cis-regulatory Sequences
10.1K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
10.1K
Translesion DNA Polymerases
10.1K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.1K


