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Nbs1-dependent binding of Mre11 to adenovirus E4 mutant viral DNA is important for inhibiting DNA replication

Shomita S Mathew1, Eileen Bridge

  • 1Department of Microbiology, 32 Pearson Hall, Miami University, Oxford, OH 45056, USA.

Virology
|February 1, 2008
PubMed

Insights

Adenovirus infections disrupt DNA repair. Viral proteins target the MRN complex, but Mre11 and Nbs1 proteins bind viral DNA, hindering replication.

Area of Science:

  • Molecular Biology
  • Virology
  • DNA Damage and Repair

Background:

  • Adenovirus (Ad) infections activate cellular DNA damage response pathways.
  • Ad early proteins target the MRN complex (Mre11, Rad50, Nbs1) for degradation, preventing DNA damage response activation.
  • Mre11 localization at DNA damage sites depends on Nbs1 and Mdc1.

Purpose of the Study:

  • To investigate the role of Mre11 and Nbs1 in Ad replication.
  • To elucidate the mechanism by which Ad proteins interfere with DNA repair pathways.

Main Methods:

  • Immunoprecipitation assays to detect protein-DNA interactions.
  • Confocal microscopy to visualize protein localization.
  • Analysis of Ad E4 mutant infections.

Main Results:

  • Nbs1 is essential for Mre11 localization at viral DNA replication foci in Ad E4 mutant infections.
  • Mre11 is crucial for Mdc1 foci formation in infected cells.
  • Mre11 and Mdc1 bind viral DNA, with Nbs1 mediating Mre11 binding.
  • Nbs1-mediated Mre11 binding to viral DNA correlates with impaired viral DNA replication.

Conclusions:

  • Nbs1 mediates the physical interaction of Mre11 with viral DNA.
  • This interaction interferes with Ad DNA replication, suggesting a novel viral strategy to manipulate host DNA repair.
  • Mre11 acts as a DNA damage sensor, and its recruitment to viral DNA by Nbs1 impacts viral replication efficiency.

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