title: Building a replisome from interacting pieces: sliding clamp complexed to a peptide from DNA polymerase and a polymerase editing complex.
abstract: We have solved the crystal structures of the bacteriophage RB69 sliding clamp, its complex with a peptide essential for DNA polymerase interactions, and the DNA polymerase complexed with primer-template DNA. The editing complex structure shows a partially melted duplex DNA exiting from the exonuclease domain at an unexpected angle and significant changes in the protein structure. The clamp complex shows the C-terminal 11 residues of polymerase bound in a hydrophobic pocket, and it allows docking of the editing and clamp structures together. The peptide binds to the sliding clamp at a position identical to that of a replication inhibitor peptide bound to PCNA, suggesting that the replication inhibitor protein p21CIP1 functions by competing with eukaryotic polymerases for the same binding pocket on the clamp.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8814, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shamoo
authors.forename: T A
authors.initials: TA
authors.lastname: Steitz
mesh_terms: D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000737:chemistry* / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013698:Templates, Genetic
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004279:DNA, Viral; D018809:Proliferating Cell Nuclear Antigen; D004259:DNA-Directed DNA Polymerase