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Journal of Virology, December 2008, p. 12574-12579, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01193-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of Homodimerization of Human Cytomegalovirus DNA Polymerase Accessory Protein UL44 in Origin-Dependent DNA Replication in Cells{triangledown}

Elisa Sinigalia,1,# Gualtiero Alvisi,2,# Beatrice Mercorelli,1 Donald M. Coen,3 Gregory S. Pari,4 David A. Jans,5 Alessandro Ripalti,6 Giorgio Palù,1* and Arianna Loregian1*

Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35121 Padua, Italy,1 Department of Hematology and Medical Oncology Seragnoli, University of Bologna, 40138 Bologna, Italy,2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,3 Department of Microbiology and Immunology and the Cell and Molecular Biology Graduate Program, University of Nevada-Reno, Reno, Nevada 89557,4 Department of Biochemistry and Molecular Biology, Monash University, 3800 Clayton, Victoria, Australia,5 Microbiology Operative Unit, St. Orsola General Hospital, University of Bologna, 40138 Bologna, Italy6

Received 9 June 2008/ Accepted 25 September 2008

The presumed processivity subunit of human cytomegalovirus (HCMV) DNA polymerase, UL44, forms homodimers. The dimerization of UL44 is important for binding to DNA in vitro; however, whether it is also important for DNA replication in a cellular context is unknown. Here we show that UL44 point mutants that are impaired for dimerization, but not for nuclear localization or interaction with the C terminus of the polymerase catalytic subunit, are not capable of supporting HCMV oriLyt-dependent DNA replication in cells. These data suggest that the disruption of UL44 homodimers could represent a novel anti-HCMV strategy.

* Corresponding author. Mailing address: Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, via Gabelli 63, 35121 Padua, Italy. Phone for Arianna Loregian: 39 049 8272363. Fax: 39 049 8272355. E-mail: arianna.loregian{at}unipd.it. Phone for Giorgio Palù: 39 049 8272350. Fax: 39 049 8272355. E-mail: giorgio.palu{at}unipd.it

{triangledown} Published ahead of print on 8 October 2008.

# These two authors contributed equally to this work.

Journal of Virology, December 2008, p. 12574-12579, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01193-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alvisi, G., Roth, D. M., Camozzi, D., Pari, G. S., Loregian, A., Ripalti, A., Jans, D. A. (2009). The Flexible Loop of the Human Cytomegalovirus DNA Polymerase Processivity Factor ppUL44 Is Required for Efficient DNA Binding and Replication in Cells. J. Virol. 83: 9567-9576 [Abstract] [Full Text]  
  • Strang, B. L., Sinigalia, E., Silva, L. A., Coen, D. M., Loregian, A. (2009). Analysis of the Association of the Human Cytomegalovirus DNA Polymerase Subunit UL44 with the Viral DNA Replication Factor UL84. J. Virol. 83: 7581-7589 [Abstract] [Full Text]  


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