人类REV1对未受损和受损DNA的催化作用
Anastasia D Stolyarenko1,2, Anna A Novikova1,2, Evgeniy S Shilkin1,2
1National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
International journal of molecular sciences
|April 13, 2024
概括
人类REV1DNA聚合酶准确地合成与8-oxoG和O6-meG病变相反的DNA. 它还复制易发生错误的乙氨基甘醇,突出其在DNA修复和合成中的作用.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 遗传学 遗传学是一种遗传学.
背景情况:
- REV1是一种支架蛋白,对DNA转化合成 (TLS) 至关重要.
- REV1具有Y家族DNA聚合酶活性,但其准确性和效率仍有争议.
- 了解REV1的功能是理解DNA修复机制的关键.
研究的目的:
- 描述全身人REV1.1的生物化学活性.
- 评估REV1在各种未损坏和损坏的DNA模板上的准确性和效率.
- 阐明REV1的基质偏好的结构基础.
主要方法:
- 来自Saccharomyces cerevisiae的全身人类REV1的表达和净化.
- 在不同DNA模板上的REV1的DNA聚合酶活性体外表征.
- 使用特定的DNA病变,包括8-oxoG,O6-meG,硫胺糖醇,青交叉链接和乙腺素.
主要成果:
- REV1表现出与8-oxoG和O6-meG相对准确的合成,效率中等.
- REV1以易发生错误的方式复制胺糖醇,并被GG青交叉链阻断.
- 生物化学数据支持模板A的Hoogsteen面对REV1活动的重要性.
结论:
- 人类REV1作为分布性DNA聚合酶,具有明显的病变特异性活动.
- REV1精确绕过某些病变的能力有助于基因组的稳定性.
- 该研究提供了关于REV1的机制及其在耐受DNA损伤中的作用的见解.
相关概念视频
Homologous Recombination
50.5K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.5K
Overview of DNA Repair
31.0K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.0K
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
Base Excision Repair
22.3K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.3K
Translesion DNA Polymerases
10.0K
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...
10.0K


