title: DNA polymerases: Hoogsteen base-pairing in DNA replication?
abstract: Human polymerase-iota belongs to the error-prone Y family of polymerases, which frequently incorporate incorrect nucleotides during DNA replication but can efficiently bypass DNA lesions. On the basis of X-ray diffraction data, Nair et al. propose that Hoogsteen base-pairing is adopted by DNA during its replication by this enzyme. Here I re-examine their X-ray data and find that the electron density is very weak for a Hoogsteen base pair formed between a template adenine deoxyribonucleotide in the syn conformation and a deoxythymidine 5'-triphosphate (dTTP), and that the fit is better for a normal Watson-Crick base pair. As a guanine-cytosine (G-C) base pair has no potential to form a Hoogsteen base pair at physiological pH, Hoogsteen base-pairing is unlikely to be used in replication by this polymerase.
authors.affiliation: Center for Structural Biology, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA wang@csb.yale.edu.
authors.forename: Jimin
authors.initials: J
authors.lastname: Wang
mesh_terms: D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D015203:Reproducibility of Results; D055672:Static Electricity; D000094769:DNA Polymerase iota
chemical_list: D004247:DNA; D004259:DNA-Directed DNA Polymerase; D000094769:DNA Polymerase iota; C000722070:POLI protein, human