title: A novel mechanism of sugar selection utilized by a human X-family DNA polymerase.
abstract: During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2'-hydroxyl group and the bulky side chain of an active-site residue. In this study, we demonstrated that human DNA polymerase lambda used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2'-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2'-position.
authors.affiliation: Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Brown
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Fiala
authors.forename: Jason D
authors.initials: JD
authors.lastname: Fowler
authors.forename: Shanen M
authors.initials: SM
authors.lastname: Sherrer
authors.forename: Sean A
authors.initials: SA
authors.lastname: Newmister
authors.forename: Wade W
authors.initials: WW
authors.lastname: Duym
authors.forename: Zucai
authors.initials: Z
authors.lastname: Suo
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D012265:Ribonucleotides; D004247:DNA; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta