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Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Homologous Recombination02:31

Homologous Recombination

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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

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Related Experiment Video

Updated: Jul 4, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing.

Rika Kusumoto1, Lala Dawut, Caterina Marchetti

  • 1Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.

Biochemistry
|June 19, 2008
PubMed
Summary

Werner protein (WRN) interacts with the DNA repair factor XRCC4-DNA ligase IV (X4L4), stimulating WRN

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Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair

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Last Updated: Jul 4, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
10:59

Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair

Published on: May 24, 2017

Area of Science:

  • Molecular Biology
  • Genetics
  • DNA Repair Mechanisms

Background:

  • Werner syndrome (WS) is a premature aging disorder linked to defects in the Werner protein (WRN).
  • WRN, a RecQ helicase, interacts with DNA metabolic and repair proteins, including Ku70/86 and DNA-PKcs.
  • Nonhomologous end-joining (NHEJ) is a critical DNA double-strand break repair pathway involving Ku70/86, DNA-PKcs, and XRCC4-DNA ligase IV (X4L4).

Purpose of the Study:

  • To investigate the interaction between Werner protein (WRN) and the NHEJ factor XRCC4-DNA ligase IV (X4L4).
  • To determine the functional consequences of the WRN-X4L4 interaction on WRN's enzymatic activities.
  • To explore the role of WRN in DNA repair pathways through its interaction with NHEJ components.

Main Methods:

  • Co-immunoprecipitation assays to demonstrate physical interaction between WRN and X4L4.
  • In vitro assays to assess the effect of X4L4 on WRN's helicase and exonuclease activities.
  • DNA end-joining assays to evaluate the functional significance of the WRN-X4L4 interaction in DNA repair.

Main Results:

  • Werner protein (WRN) physically interacts with XRCC4-DNA ligase IV (X4L4).
  • X4L4 stimulates the exonuclease activity of WRN but does not affect its helicase activity.
  • Unlike WRN, the related RecQ helicase BLM does not bind X4L4, and its helicase activity is unaffected by X4L4.
  • WRN-processed DNA substrates are efficiently ligated by X4L4 in DNA end-joining assays, supporting a functional interaction.

Conclusions:

  • Werner protein (WRN) directly interacts with XRCC4-DNA ligase IV (X4L4), a key component of the NHEJ pathway.
  • This interaction modulates WRN's exonuclease activity, suggesting a role in processing DNA breaks for repair.
  • The findings highlight a novel functional link between WRN and the NHEJ machinery, potentially contributing to genomic stability in Werner syndrome.