4ruc

Publication Abstract from PubMed

N(6)-(2-Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylf ormamidopyrimidine (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 eta and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The structures of the hPol eta 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.

Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG Lesion by Human DNA Polymerase eta and Sulfolobus solfataricus P2 Polymerase IV.,Patra A, Banerjee S, Johnson Salyard TL, Malik CK, Christov PP, Rizzo CJ, Stone MP, Egli M J Am Chem Soc. 2015 Jun 10;137(22):7011-4. doi: 10.1021/jacs.5b02701. Epub 2015, May 27. PMID:25988947^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.