易发生错误的DNA聚合酶的适应性使用在瘤发生过程中为基因组复制提供了灵活性
Lewis J Bainbridge1, Yasukazu Daigaku1
1Cancer Genome Dynamics Project, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer science
|April 23, 2024
概括
癌细胞利用易发生错误的DNA聚合酶进行复制,加速突变和化学抵抗. 了解这些机制为癌症治疗提供了潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症生物学 癌症生物学
背景情况:
- DNA聚合酶对于精确的DNA复制和基因组维护至关重要.
- 细胞复制需要准确性和灵活性之间的平衡,容易出错的聚合酶提供了灵活性.
- 在癌症中常见的DNA复制障碍需要增加灵活性.
研究的目的:
- 审查最近对聚合酶使用在瘤发生过程中如何改变的理解.
- 检查改变聚合酶使用对癌细胞存活率和瘤进展的影响.
- 探索调控机制,比如Rad18介导的PCNA无处不在,影响易发生错误的聚合酶功能.
主要方法:
- 文献综述专注于癌症中的DNA聚合酶.
- 对控制聚合酶活性的调控机制的分析.
- 检查聚合酶在瘤基因诱导的复制应激和BRCA缺乏症中的作用.
主要成果:
- 癌细胞利用易出错的聚合酶在压力下维持复制,尽管有可能发生突变.
- 改变聚合酶的使用,而不仅仅是表达水平,是癌症的关键.
- 监管机制,如PCNA无处不在,影响易出错的聚合酶的功能化.
结论:
- 癌细胞依赖于易发生错误的聚合酶在瘤性压力下进行复制,加速突变发生并赋予化学抵抗.
- 这种依赖带来了潜在的治疗脆弱性.
- 准聚合酶使用机制可以提供新的癌症治疗策略.
相关概念视频
Proofreading
6.3K
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...
6.3K
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
Genome Copying Errors
4.2K
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.
4.2K
The DNA Replication Fork
35.9K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
35.9K
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
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


