有效的双链断裂修复需要暂时的RNA-DNA混合体
Corina Ohle1, Rafael Tesorero1, Géza Schermann1
1Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Cell
|November 25, 2016
概括
在DNA修复过程中, RNase H酶降解这些混合体,确保DNA双链断裂修复过程中的基因组稳定性.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 已知RNA-DNA混合物会导致DNA损伤.
- 通过RNase H酶降解RNA-DNA杂交物对基因组稳定性至关重要.
研究的目的:
- 研究RNA-DNA混合体和RNase H酶在DNA修复中的作用.
- 阐明同源重组 (HR) 介导的DNA双链断裂 (DSB) 修复的机制.
主要方法:
- 在Schizosaccharomyces pombe中使用特定的DSB系统.
- 分析了RNase H删除和过度表达对RNA-DNA混合稳定性和DNA修复过程的影响.
- 评估了SSDNA结合RPA复合物的使用情况.
主要成果:
- 在HR介导的DSB修复过程中形成RNA-DNA杂交.
- 通过降解这些混合物,RNase H酶对于有效的DSB修复至关重要.
- 删除RNase H使混合体稳定,从而损害了RPA的招募.
- 过度表达RNase H1使混合体不稳定,导致过度切除和重复损失.
结论:
- RNA-DNA混合体在同源重组中介的DNA修复中发挥着功能性作用.
- 在DSB修复过程中,RNase H酶是RNA-DNA杂交水平的关键调节者.
- 这项研究挑战了现有的HR模型,并强调了RNA-DNA混合体在维持基因组稳定性方面的新角色.
相关概念视频
Homologous Recombination
64.9K
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...
64.9K
Homologous Recombination
7.1K
7.1K
Fixing Double-strand Breaks
15.8K
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...
15.8K
Fixing Double-strand Breaks
4.6K
4.6K
Translesion DNA Polymerases
11.5K
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...
11.5K
Mismatch Repair
6.9K
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...
6.9K


