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関連する概念動画

The Replisome03:01

The Replisome

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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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Replication in Eukaryotes02:31

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Replication in Eukaryotes01:29

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
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DNA Replication02:40

DNA Replication

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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication...
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SARS-CoV-2ポリメラーゼの複製構造

Hauke S Hillen1, Goran Kokic1, Lucas Farnung1

  • 1Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

Nature
|May 22, 2020
PubMed
まとめ

SARS-CoV-2のRNA依存RNAポリメラーゼ (RdRp) 複合体の冷凍電子顕微鏡構造を決定しました. この構造は酵素がウイルスゲノムを複製する方法を明らかにし,抗ウイルス薬のメカニズムについての洞察を提供します.

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科学分野:

  • 構造生物学
  • ウイルス学
  • 分子生物学

背景:

  • 重症急性呼吸器症候群コロナウイルス2型 (SARS-CoV-2型) は,ゲノム複製および遺伝子転写のためにRNA依存型RNAポリメラーゼ (RdRp) に依存しています.
  • SARS-CoV-2 RdRpの構造を理解することは,COVID-19に対する抗ウイルス治療の開発に不可欠です.

研究 の 目的:

  • SARS-CoV-2 RdRpの活性複製形態の冷凍電子顕微鏡構造を提示する.
  • RdRpのプロセシビティとRNAとの相互作用の構造的基礎を解明する.
  • SARS-CoV-2 RdRpを標的とした抗ウイルス薬の作用メカニズムに関する洞察を提供すること.

主な方法:

  • 低温電子顕微鏡 (cryo-EM) を使用して,SARS-CoV-2 RdRp複合体の高解像度構造を決定した.
  • 構造には,ウイルスタンパク質 nsp12,nsp8,nsp7,RNAテンプレート-プロダクトデュプレックスが含まれています.

主要な成果:

  • 構造は,RNAテンプレートに結合するnsp12の活性部位の裂け目を明らかにし,RdRp活動を媒介する.
  • 2つのnsp8分子は裂け目に結合し,RNAを位置づけ,プロセシビティを高める"滑りポール"を特徴としています.
  • 観察された構造は,RdRpの機能と抑制を理解するための詳細な分子基盤を提供します.

結論:

  • 活性SARS-CoV-2 RdRp複合体の決定された構造は,ウイルスRNA複製の詳細な分子理解を提供します.
  • nsp8の"滑動極"は,長いコロナウイルスゲノムの複製に不可欠な酵素のプロセス性を説明します.
  • この構造情報は,レムデシビルのような抗ウイルス薬のSARS-CoV-2に対する抑制メカニズムの分析を容易にする.