The human cytomegalovirus UL44 C clamp wraps around DNA.
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.
Komazin-Meredith
Gloria
G
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Petrella
Robert J
RJ
Santos
Webster L
WL
Filman
David J
DJ
Hogle
James M
JM
Verdine
Gregory L
GL
Karplus
Martin
M
Coen
Donald M
DM
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*
D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D046911:Macromolecular Substances; D014764:Viral Proteins; D004247:DNA; D004259:DNA-Directed DNA Polymerase