The carboxy-terminal segment of the human cytomegalovirus DNA polymerase accessory subunit UL44 is crucial for viral replication.
The amino-terminal 290 residues of UL44, the presumed processivity factor of human cytomegalovirus DNA polymerase, possess all of the established biochemical activities of the full-length protein, while the carboxy-terminal 143 residues contain a nuclear localization signal (NLS). We found that although the amino-terminal domain was sufficient for origin-dependent synthesis in a transient-transfection assay, the carboxy-terminal segment was crucial for virus replication and for the formation of DNA replication compartments in infected cells, even when this segment was replaced with a simian virus 40 NLS that ensured nuclear localization. Our results suggest a role for this segment in viral DNA synthesis.
Silva
Laurie A
LA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Loregian
Arianna
A
Pari
Gregory S
GS
Strang
Blair L
BL
Coen
Donald M
DM
D000595:Amino Acid Sequence; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections; D004279:DNA, Viral / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D006801:Humans; D019913:Nuclear Localization Signals; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D019913:Nuclear Localization Signals; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase