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Related Concept Videos

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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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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The DNA Replication Fork01:02

The DNA Replication Fork

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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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S-Cdk Initiates DNA Replication02:38

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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
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Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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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...
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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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Updated: Nov 8, 2025

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Inhibition of DNA replication initiation by silver nanoclusters.

Yu Tao1, Tomas Aparicio1, Mingqiang Li2

  • 1Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.

Nucleic Acids Research
|April 27, 2021
PubMed
Summary
This summary is machine-generated.

Silver nanoclusters (AgNCs) uniquely inhibit DNA replication by directly blocking the MCM complex loading, preventing pre-replication complex assembly. This discovery offers a new tool for studying DNA replication.

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Area of Science:

  • Nanomaterials Science
  • Molecular Biology
  • Cell Biology

Background:

  • Silver nanoclusters (AgNCs) possess unique physicochemical properties enabling interactions with biomolecules like proteins and DNA.
  • AgNCs are increasingly explored for diagnostic and therapeutic applications, necessitating an understanding of their cellular effects.

Purpose of the Study:

  • To investigate the impact of AgNCs on DNA replication and the DNA damage response in cell-free extracts.
  • To elucidate the mechanism by which AgNCs affect DNA replication.

Main Methods:

  • Utilized cell-free extracts from Xenopus laevis eggs to study DNA replication.
  • Employed FLAG-AgNCs immunoprecipitation and mass spectrometry to identify interacting proteins.
  • Assessed effects on genomic DNA replication, DNA replication checkpoint, nuclear membrane, and nucleosome assembly.

Main Results:

  • AgNCs uniquely inhibited genomic DNA replication and abrogated the DNA replication checkpoint.
  • AgNCs did not interfere with nuclear membrane or nucleosome assembly.
  • A significant defect in the loading of the mini-chromosome maintenance (MCM) complex was observed in AgNCs-supplemented extracts.
  • Direct interaction between AgNCs and the MCM complex was confirmed, showing AgNCs prevent MCM loading and pre-replication complex assembly.

Conclusions:

  • AgNCs directly inhibit DNA replication initiation by preventing MCM complex loading and pre-replication complex assembly.
  • AgNCs represent a novel tool for studying chromosomal DNA replication mechanisms.
  • Findings expand the potential experimental applications of silver nanomaterials.