Related Experiment Video

Updated: Aug 3, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Relocalization of the Mre11-Rad50-Nbs1 complex by the adenovirus E4 ORF3 protein is required for viral replication

Jared D Evans1, Patrick Hearing

  • 1Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York 11794-5222, USA.

Journal of Virology
|April 29, 2005
PubMed

Insights

Adenovirus E4 ORF3 protein relocates PML and MRN complexes, crucial for viral DNA replication. This viral protein manipulates nuclear organization to promote virus growth.

Area of Science:

  • Molecular Virology
  • Cellular Biology
  • DNA Damage Response

Background:

  • Adenovirus replication relies on nuclear protein complex reorganization.
  • Promyelocytic leukemia protein (PML) nuclear domains and Mre11-Rad50-Nbs1 (MRN) are key players.
  • Viral proteins can manipulate host cell machinery.

Purpose of the Study:

  • To investigate the role of Adenovirus E4 ORF3 protein in nuclear protein complex relocalization.
  • To determine the impact of E4 ORF3 on PML and MRN localization during infection.
  • To understand how viral regulation of these complexes affects viral replication.

Main Methods:

  • Analysis of viral mutants and protein localization via microscopy.
  • Studying protein colocalization with E4 ORF3.
  • Complementation assays in cells lacking MRN components.

Main Results:

  • E4 ORF3 protein causes relocalization and colocalization of PML and MRN early in infection.
  • MRN reorganization correlates with viral DNA replication domain establishment.
  • MRN reorganization can be independent of PML rearrangement; MRN components redistribute and Mre11 is degraded later.
  • E4 mutant viruses show impaired growth in Mre11 or Nbs1 deficient cells.

Conclusions:

  • Adenovirus E4 ORF3 protein is essential for regulating nuclear organization to facilitate viral replication.
  • E4 ORF3 manipulates both PML nuclear bodies and the MRN complex.
  • Targeting host DNA repair machinery is a key viral strategy for promoting replication.

More Related Videos

Rescue of Recombinant Newcastle Disease Virus from cDNA10:55

Rescue of Recombinant Newcastle Disease Virus from cDNA

Published on: October 12, 2013

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells10:22

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells

Published on: November 12, 2015

Related Concept Videos

Mismatch Repair01:36

Mismatch 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...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
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...
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...