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関連する概念動画

Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

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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...
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Overview of DNA Repair02:25

Overview of DNA Repair

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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...
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Nucleotide Excision Repair01:08

Nucleotide Excision Repair

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Homologous Recombination02:31

Homologous Recombination

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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...
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DNA Damage can Stall the Cell Cycle02:37

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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...
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Translesion DNA Polymerases02:10

Translesion DNA Polymerases

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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...
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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
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DNAダメージはDuplex-G-Quadruplex-Duplex文脈でG-四重折り畳みを加速する

Aaron M Fleming1, Brandon Leonel Guerra Castañaza Jenkins1, Bethany A Buck1

  • 1Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.

Journal of the American Chemical Society
|April 11, 2024
PubMed
まとめ

DNAの損傷は潜在的なG四重複配列 (PQS) の折り畳みに大きく影響し,遺伝子調節に影響します. DNAの断裂はPQSの折り畳みを加速し 細胞の複製や修復に 影響を及ぼします

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A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
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A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
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科学分野:

  • 分子生物学
  • 遺伝学
  • 生物化学

背景:

  • 潜在的なG四重複配列 (PQS) は,遺伝子調節に不可欠な非正規のDNA構造を形成する.
  • PQSの折りたたみ運動に対するDNA損傷の影響は,まだ十分に理解されていません.
  • PQSの折りたたみに関するゲノムDNAの制約は,デュプレックス-G-クアドルプレックス-デュプレックス (DGD) 構造で模倣される.

研究 の 目的:

  • PQSの折りたたみ運動に対するDNA塩基損傷と鎖の断裂の影響を調査する.
  • VEGFプロモーター配列を用いて,DGDの支架内のPQSの折り畳みを分析する.
  • 細胞時間スケールに関連するPQSの折りたたみに対する損傷の影響を決定する.

主な方法:

  • 折りたたみ運動をモニターするための円形二重化 (CD) スペクトロスコーピー.
  • 構造分析のための1Dプロトン核磁気共鳴 (1H NMR)
  • VEGFプロモーター配列のデュプレックス-G-クアドルプレックス-デュプレックス (DGD) 構造を用いる.

主要な成果:

  • 折り畳み半減期は,DNAの損傷の種類と位置によって2秒から12分まで変化しました.
  • G-ランの近くの単一ストランドの断裂は,折り畳みを150倍以上加速した.
  • Mg2+イオンとAPE1タンパク質はPQSの折りたたみを促進した.
  • CDとNMRでG4の形成と 損傷による折りたたみが確認されました

結論:

  • DNAの損傷,特に鎖の断裂は,PQSの折りたたみ運動を大きく変化させます.
  • VEGFプロモーターのPQSの折り畳みは,DNAの損傷の種類と位置に敏感です.
  • 測定された折り畳み半減期は,DNA複製,転写,および修復プロセスに関連しています.