Translesion synthesis of abasic sites by yeast DNA polymerase epsilon.
Studies of replicative DNA polymerases have led to the generalization that abasic sites are strong blocks to DNA replication. Here we show that yeast replicative DNA polymerase epsilon bypasses a model abasic site with comparable efficiency to Pol eta and Dpo4, two translesion polymerases. DNA polymerase epsilon also exhibited high bypass efficiency with a natural abasic site on the template. Translesion synthesis primarily resulted in deletions. In cases where only a single nucleotide was inserted, dATP was the preferred nucleotide opposite the natural abasic site. In contrast to translesion polymerases, DNA polymerase epsilon with 3'-5' proofreading exonuclease activity bypasses only the model abasic site during processive synthesis and cannot reinitiate DNA synthesis. This characteristic may allow other pathways to rescue leading strand synthesis when stalled at an abasic site.
Department of Medical Biochemistry and Biophysics, Umeå University, SE 901 87 Umeå, Sweden.
Nasim
N
Sabouri
Erik
E
Johansson
D004249:DNA Damage; D004257:DNA Polymerase II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D005663:Furans / Q000737:chemistry; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D000099270:Y-Family DNA Polymerases
D004257:DNA Polymerase II; D019951:DNA Polymerase beta; D017931:DNA Primers; D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D005663:Furans; D005982:Glutathione Transferase; D011993:Recombinant Fusion Proteins; C018674:tetrahydrofuran; C509838:Dpo4 protein, E coli; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases