title: Human DNA polymerases lambda and beta show different efficiencies of translesion DNA synthesis past abasic sites and alternative mechanisms for frameshift generation.
abstract: Human DNA polymerases (pols) beta and lambda could promote template slippage and generate -1 frameshifts on defined heteropolymeric DNA substrates containing a single abasic site. Kinetic data demonstrated that pol lambda was more efficient than pol beta in catalyzing translesion DNA synthesis past an abasic site, particularly in the presence of low nucleotide concentrations. Moreover, pol lambda was found to generate frameshifts in two ways: first, by using a nucleotide-stabilized primer misalignment mechanism, or second, by promoting primer reannealing using microhomology regions between the terminal primer sequence and the template strand. Our results suggest a molecular mechanism for the observed high in vivo rate of frameshifts generation by pol lambda and highlight the remarkable ability of pol lambda to promote microhomology pairing between two DNA strands, further supporting its proposed role in the nonhomologous end joining process.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 Toulouse Cedex, France.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Blanca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villani
authors.forename: Igor
authors.initials: I
authors.lastname: Shevelev
authors.forename: Kristijan
authors.initials: K
authors.lastname: Ramadan
authors.forename: Silvio
authors.initials: S
authors.lastname: Spadari
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hübscher
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D004261:DNA Replication; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D016368:Frameshift Mutation; D005663:Furans / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D012091:Repetitive Sequences, Nucleic Acid; D013379:Substrate Specificity; D013698:Templates, Genetic
chemical_list: D017931:DNA Primers; D005663:Furans; C018674:tetrahydrofuran; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase