Defects in base excision repair combined with elevated intracellular dCTP levels dramatically reduce mutation induction in yeast by ethyl methanesulfonate and N-methyl-N′-nitro-N-nitrosoguanidine
✍ Scribed by Bernard A. Kunz; Elizabeth S. Henson; Ramachandran Karthikeyan; Theodore Kuschak; Shelley A. McQueen; Catherine A. Scott; Wei Xiao
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 153 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Previously, we determined that elimination of de-EMS or MNNG induction of total SUP4-o mutations, oxycytidylate (dCMP) deaminase (DCD1) in the GrC r ArT transitions and GrC r CrG transveryeast Saccharomyces cerevisiae increases the intra-sions were reduced by ú98%, ú97%, and ú80%, cellular dCTP:dTTP ratio and reduces the induction respectively. Mutation frequencies in the dcd1 apn1 of GrC r ArT transitions in the SUP4-o gene by strain were close to those for spontaneous mutagenethyl methanesulfonate (EMS) and N-methyl-Nesis in the wild-type parent. These findings argue nitro-N-nitrosoguanidine (MNNG). Simultaneously, that misincorporation of dCTP during repair of alkylthe GrC r CrG transversion frequency rises sub-ation-induced AP sites is responsible for the instantially. We attributed the first response to dCTP creased GrC r CrG transversion frequency in the outcompeting dTTP for incorporation opposite O 6 -dcd1 strain treated with EMS or MNNG. The data alkylguanine, and the second outcome to the in-also demonstrate that defective repair of AP sites creased dCTP pool causing error-prone repair of coupled with an elevated dCTP:dTTP ratio elimiapurinic (AP) sites resulting from the removal or la-nates most EMS and MNNG mutagenesis. In addibility of N 7 -alkylguanine. To test the latter hypothe-tion, the results point to a role for AP sites in the sis, we used isogenic dcd1 strains deleted for either production of some EMS-and MNNG-induced of two genes (MAG1: 3-methyladenine glycosy-GrC r ArT transitions as well as other substitutions lase; APN1: apurinic endonuclease) involved in the in the dcd1 strain.