迪诺科克菌蛋白酶PprI通过直接与单链DNA相互作用来感知DNA损伤
Huizhi Lu1, Zijing Chen1, Teng Xie1,2
1MOE Key Laboratory of Biosystems Homeostasis & Protection, Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, China.
Nature communications
|February 29, 2024
概括
单链DNA通过结合PprI蛋白酶激活细菌DNA损伤反应,增强其与DdrO抑制剂的相互作用. 这揭示了一个新的SOS独立的细菌生存和耐药性的途径.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细菌拥有应激反应系统以适应.
- 在Deinococcus中,DNA损伤反应涉及金属酶PprI分裂抑制剂DdrO.
- 这种PprI-DdrO系统被激活的上游信号以前是未知的.
研究的目的:
- 为了识别上游调节信号,激活基于PprI-DdrO蛋白酶的DNA损伤反应系统.
- 阐明这个信号激活系统的机制.
- 探索对细菌生存和耐药性的影响.
主要方法:
- 在体内和体外的生物化学测试来研究蛋白质相互作用和裂变.
- 在阿波和单链DNA结合状态下对PprI的结构分析.
- 研究PprI单体-二元平衡及其对活性的影响.
主要成果:
- 单链DNA与PprI蛋白酶进行物理相互作用.
- 这种相互作用以长度依赖的方式增强了PprI-DdrO相互作用和DdrO裂变.
- 结构数据揭示了PprI上的DNA结合接口,这些接口塑造了分裂部位.
- PprI的动态单体-二元平衡对其分裂活动至关重要.
结论:
- 单链DNA作为细菌金属蛋白酶/抑制系统中DNA损伤感应的上游信号.
- 这一发现为细菌在压力下生存的新型SOS独立途径提供了洞察力.
- 这些发现可能解释细菌生存和获得的耐药性机制.
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
Single-Strand DNA Binding Proteins
14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.1K
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
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
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
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


