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関連する概念動画

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

14.9K
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...
14.9K
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

10.1K
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...
10.1K
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,...
5.9K
Homologous Recombination02:31

Homologous Recombination

51.4K
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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Condensins02:15

Condensins

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Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
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Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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Transition metal activation reframes SAMHD1 regulation.

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Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.

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関連する実験動画

Updated: Sep 8, 2025

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
08:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

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ssDNAとssRNAはSAMHD1の相凝縮を促進する

Brandon E Smith1, Ankita Pohnerkar1, Benjamin Orris1

  • 1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States.

Biochemistry
|September 6, 2025
PubMed
まとめ

SAMHD1タンパク質は,GTPによって調節される核酸で液体状の滴状に凝縮されます. この液体-液体相分離 (LLPS) は,がんとウイルス感染症の治療に意味があります.

科学分野:

  • 生化学と分子生物学
  • 細胞生物学
  • 構造生物学

背景:

  • SAMHD1 (SAMドメインおよびHDドメインを含むタンパク質1) は,ウイルス制限およびDNA修復を含む多様な役割を持つdNTPaseである.
  • SAMHD1の機能は液体-液体相分離 (LLPS) を含むが,それ自身の相分離特性は以前は特徴づけられていなかった.
  • タンパク質のテトラメリック構造は,GTP結合によってアロステリックに活性化され,核酸との相互作用に影響する.

研究 の 目的:

  • SAMHD1が液体-液体相分離 (LLPS) を受ける可能性を調査する.
  • SAMHD1相分離に関わる条件と領域を特徴づける.
  • SAMHD1 LLPSの生物学的関連性と治療の可能性を調査する.

主な方法:

  • MolPhase を使用した相分離傾向の計算予測.
  • PEG 2000,ssDNA,ssRNAを用いたインビトロ相分離試験
  • ドメイン固有の貢献 (SAMとCTドメイン) とリガンド効果 (GTP,dGTP) の生化学分析.
  • SAMHD1-ssDNA凝縮体を観察するためのヒト細胞における微量注射実験.

主要な成果:

  • SAMHD1は中程度の相分離確率 (0. 65) を示し,SAMとCTドメインが鍵となると予測されています.

さらに関連する動画

Chemical Dimerization-Induced Protein Condensates on Telomeres
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Chemical Dimerization-Induced Protein Condensates on Telomeres

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Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
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Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

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関連する実験動画

Last Updated: Sep 8, 2025

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
08:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

2.5K
Chemical Dimerization-Induced Protein Condensates on Telomeres
08:52

Chemical Dimerization-Induced Protein Condensates on Telomeres

Published on: April 12, 2021

3.2K
Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
09:43

Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

2.4K
  • In vitroでは,SAMHD1は,ドメインの削除またはA1サイトリガンドによって破壊されたPEG 2000の存在で,ssDNA/ssRNAで液体状のドロップルを形成した.
  • SAMHD1- ssDNA凝縮体はヒト細胞の核内で観察され,生物学的関連性を示した.
  • 結論:

    • SAMHD1は,特に核酸の存在下で,特定の条件下で液体液相分離 (LLPS) を受けることができます.
    • SAMとCTドメインはSAMHD1LLPSにとって不可欠であり,A1サイトリガンドはこれらの凝縮体を調節する.
    • SAMHD1 LLPSは,がんやウイルス感染症の新たな治療標的となる可能性を秘めています.