在尼克酶破碎的复制分叉中,单端和双端断裂
Ralph Scully1, Johannes C Walter2, André Nussenzweig3
1Department of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
DNA repair
|November 6, 2024
概括
DNA复制错误可能导致双链断裂 (DSB). 修复这些断裂,特别是复制叉上的单端DSB,可能有利于同源重组,影响癌症和基因编辑.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 复制相关的双链断裂 (DSB) 发生在DNA复制机器遇到破裂时.
- 这些DSB的修复对于预防基因组不稳定性,癌症发作和有效的基因编辑至关重要.
研究的目的:
- 研究复制相关的DSBs的形成和修复结果.
- 了解细胞环境如何影响不同DNA修复途径之间的选择.
主要方法:
- 对DNA复制叉动态的分析.
- 破坏复制叉环境的生物化学特征.
- 评估DNA修复途径的利用情况.
主要成果:
- 与破裂的DNA发生重复体碰撞可以产生单端 (se) 和双端 (de) 的DSB.
- 哺乳动物复制叉的细胞环境似乎促进同源的重组,而不是非同源的末端连接用于DSB修复.
结论:
- DSB的类型 (se或de) 影响修复路径的选择.
- 哺乳动物细胞可能在破碎的复制分叉处拥有专门的机制,有利于同源重组,影响基因组稳定性和治疗策略.
相关概念视频
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
The DNA Replication Fork
35.6K
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...
35.6K
Fixing Double-strand Breaks
12.3K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.3K
Homologous Recombination
50.2K
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...
50.2K
Mismatch Repair
4.8K
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...
4.8K
Translesion DNA Polymerases
9.9K
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...
9.9K


