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The cellular Mre11 protein interferes with adenovirus E4 mutant DNA replication
Shomita S Mathew1, Eileen Bridge
1Department of Microbiology, 32 Pearson Hall, Miami University, Oxford OH 45056, USA.
Virology
|May 5, 2007
Summary
Adenovirus type 5 hijacks the host DNA repair protein Mre11, hindering viral DNA replication. Reducing Mre11 levels rescues replication, indicating Mre11 inhibits this process independently of genome concatenation.
Area of Science:
- Virology
- Molecular Biology
- DNA Repair
Background:
- Adenovirus type 5 (Ad5) infection involves complex interactions with host cell machinery.
- The DNA repair protein Mre11 plays a role in viral genome concatenation during Ad5 replication.
- The mediator of DNA damage checkpoint 1 (Mdc1) is known to interact with Mre11 at DNA damage sites.
Purpose of the Study:
- To investigate the specific role of Mre11 in the DNA replication defect observed in Ad5 E4 mutants.
- To determine if Mre11's inhibition of viral DNA replication is dependent on viral genome concatenation.
- To explore the involvement of Mdc1 in the Ad5 replication process and its interaction with Mre11.
Main Methods:
- RNA interference (RNAi) was used to knockdown Mre11 and Mdc1 expression.
- Viral DNA replication levels were assessed in cells with altered Mre11 or Mdc1 levels.
- Immunofluorescence was employed to observe the localization of Mre11 and Mdc1 during viral infection.
Main Results:
- RNAi-mediated knockdown of Mre11 significantly rescued the Ad5 E4 mutant DNA replication defect.
- Mre11's inhibitory effect on viral DNA replication was observed independently of viral genome concatenation.
- Mdc1 foci formation occurred during Ad5 infection, but Mdc1 knockdown did not rescue viral replication or prevent Mre11 localization.
Conclusions:
- Mre11 actively inhibits viral DNA replication when localized at viral replication centers.
- The DNA damage response protein Mdc1 is activated by Ad5 infection but does not mediate Mre11's inhibitory function.
- These findings elucidate a novel mechanism by which Ad5 manipulates host DNA repair proteins to regulate viral replication.
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