通过DNA聚合酶β在核体中的填空DNA合成的结构基础
bioRxiv : the preprint server for biology
|November 22, 2024
概括
基因聚合酶β (Pol β) 修复核体内的DNA缺口,但其机制尚不清楚. 这项研究揭示了Pol β如何塑造DNA以识别差距,并表明修复效率取决于核细胞体内的差距位置.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 单链断裂 (SSB) 是一种常见的DNA损伤.
- DNA聚合酶β (Pol β) 对于通过基切除修复 (BER) 和直接单链断裂修复 (SSBR) 在染色质中修复SSB至关重要.
- 在核子体内处理1核酸缺口的Pol β的机制尚不清楚.
研究的目的:
- 阐明核子体内的Pol β介导的填空DNA合成的动力和结构机制.
- 了解Pol β如何在染色质的背景下识别和处理1核酸缺口.
主要方法:
- 生物化学测试被用来分析Pol β活动的动力学.
- 低温电子显微镜 (cryo-EM) 用于确定与核细胞DNA结合的Pol β的高分辨率结构.
- 动力分析和结构研究被结合起来,以了解机制.
主要成果:
- 通过Pol β填补缺口的DNA合成在核细胞体内取决于位置,溶剂暴露的缺口比基因素遮蔽的缺口更有效地修复.
- 冷EM结构揭示了一个DNA雕塑机制,涉及Pol β域的顺序参与以识别差距.
- 结构数据定义了Pol β在核细胞DNA中的位置依赖核酸插入的基础.
结论:
- 这项研究确定了Pol β在DNA修复过程中处理核体中的1核酸缺口的机制.
- 提供了对染色体复杂环境中的DNA修复过程的基本见解.
相关概念视频
The Replisome
33.0K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
33.0K
Replication in Eukaryotes
170.3K
Overview
170.3K
DNA Replication
48.8K
DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied. After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication...
Replication in Prokaryotes
DNA replication...
48.8K
Proofreading
6.2K
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...
6.2K
Lagging Strand Synthesis
49.7K
During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
49.7K
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K


