title: The human cytomegalovirus UL44 C clamp wraps around DNA.
abstract: Processivity factors tether the catalytic subunits of DNA polymerases to DNA so that continuous synthesis of long DNA strands is possible. The human cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer intermediate in structure between monomeric herpes simplex virus UL42, which binds DNA directly via a basic surface, and the trimeric sliding clamp PCNA, which encircles DNA. To investigate how UL44 interacts with DNA, calculations were performed in which a 12 bp DNA oligonucleotide was docked to UL44. The calculations suggested that UL44 encircles DNA, which interacts with basic residues both within the cavity of the C clamp and in flexible loops of UL44 that complete the "circle." The results of mutational and crosslinking studies were consistent with this model. Thus, UL44 is a "hybrid" of UL42 and PCNA: its structure is intermediate between the two and its mode of interaction with DNA has elements of both.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Komazin-Meredith
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Petrella
authors.forename: Webster L
authors.initials: WL
authors.lastname: Santos
authors.forename: David J
authors.initials: DJ
authors.lastname: Filman
authors.forename: James M
authors.initials: JM
authors.lastname: Hogle
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Verdine
authors.forename: Martin
authors.initials: M
authors.lastname: Karplus
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
mesh_terms: D003587:Cytomegalovirus / Q000201:enzymology*; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D046911:Macromolecular Substances; D014764:Viral Proteins; D004247:DNA; D004259:DNA-Directed DNA Polymerase