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相关概念视频

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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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,...
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The DNA Replication Fork01:02

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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...
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The Replisome03:01

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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
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Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System
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EEPD1进化出了一种独特的DNA紧模块,保护反向复制叉.

Runze Shen1, Altaf H Sarker2, Yue Chen3

  • 1Department of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.

Nucleic acids research
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概括

意想不到,EEPD1蛋白紧,而不是裂开,DNA在复制分叉. 这一功能在氧化应激期间保护基因组稳定性,并影响癌症患者的存活率.

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科学领域:

  • 分子生物学分子生物学
  • 结构生物学 结构生物学
  • 基因组学就是基因组学.

背景情况:

  • 外核酶/内核酶/酸酶 (EEP) 折叠酸酶通常是单体二酶.
  • 以前,EEPD1在DNA应激反应中的作用及其核酶活动尚不清楚.

研究的目的:

  • 在停滞的DNA复制分叉中定义EEPD1的结构,组合和功能.
  • 阐明EEPD1在DNA复制叉保护中的机制.

主要方法:

  • 混合结构方法 (SAXS,晶体,冷EM)
  • 生物化学 生物化学
  • 进化分析是一种进化分析.
  • 癌症基因组学 癌症基因组学
  • 分子和细胞生物学分子和细胞生物学.

主要成果:

  • EEPD1形成了一个二元体,利用独特的EEP和串联的Helix-hairpin-Helix域,在反向复制叉上紧双链DNA.
  • 结构研究揭示了一个不寻常的托握手模分器,一个保存的di-Trp-Pro口袋和一个结构开关.
  • 由于进化的催化残留物损失,EEPD1缺乏内在核酶活性;它防止了MRE11介导的逆叉的降解.
  • 癌症生物信息学表明,EEPD1关联与患者的生存相关,特别是在氧化损伤的背景下.

结论:

  • EEPD1的功能是作为DNA,而不是核酶,以保护反向复制叉.
  • 这种紧机制对于甲动物的氧化应激反应和保持基因组稳定性至关重要.
  • 在叉子保护中EEPD1的作用对癌症结果和基因组稳定性有影响.