The Human Cytomegalovirus UL44 C Clamp Wraps around DNA

Gloria Komazin-Meredith, Robert J. Petrella, Webster L. Santos, David J. Filman, James M. Hogle, Gregory L. Verdine, Martin Karplus, Donald M. Coen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1214-1225
Number of pages12
JournalStructure
Volume16
Issue number8
DOIs
StatePublished - Aug 6 2008

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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