title: Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG Lesion by Human DNA Polymerase η and Sulfolobus solfataricus P2 Polymerase IV.
abstract: N(6)-(2-Deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG) arises from N7-methylation of deoxyguanosine followed by imidazole ring opening. The lesion has been reported to persist in animal tissues. Previous in vitro replication bypass investigations of the MeFapy-dG adduct revealed predominant insertion of C opposite the lesion, dependent on the identity of the DNA polymerase (Pol) and the local sequence context. Here we report crystal structures of ternary Pol·DNA·dNTP complexes between MeFapy-dG-adducted DNA template:primer duplexes and the Y-family polymerases human Pol η and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The structures of the hPol η and Dpo4 complexes at the insertion and extension stages, respectively, are representative of error-free replication, with MeFapy-dG in the anti conformation and forming Watson-Crick pairs with dCTP or dC.
authors.affiliation: †Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
authors.forename: Amritraj
authors.initials: A
authors.lastname: Patra
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.|§Northeastern Collaborative Access Team and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Building 436E, Argonne, Illinois 60439, United States.
authors.forename: Surajit
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Johnson Salyard
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Chanchal K
authors.initials: CK
authors.lastname: Malik
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Plamen P
authors.initials: PP
authors.lastname: Christov
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Carmelo J
authors.initials: CJ
authors.lastname: Rizzo
authors.affiliation: ‡Department of Chemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Stone
authors.affiliation: †Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Egli
mesh_terms: D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003849:Deoxyguanosine / Q000737:chemistry*; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry*; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D003849:Deoxyguanosine; D011743:Pyrimidines; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases