Role of homodimerization of human cytomegalovirus DNA polymerase accessory protein UL44 in origin-dependent DNA replication in cells.
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.
Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, via Gabelli 63, 35121 Padua, Italy.
Elisa
E
Sinigalia
Gualtiero
G
Alvisi
Beatrice
B
Mercorelli
Donald M
DM
Coen
Gregory S
GS
Pari
David A
DA
Jans
Alessandro
A
Ripalti
Giorgio
G
Palù
Arianna
A
Loregian
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D009154:Mutation / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D014764:Viral Proteins