Abstract
The mismatch repair pathway involves multiple proteins that are required to correct DNA polymerase generated mismatches before they become mutations. It has been shown recently, that the predominant base-pair substitution events leading to loss of endogenous Aprt activity in Pms2 null mouse cells are A:T→G:C mutations (Oncogene 21 (2002) 1768, Oncogene 21 (2002) 2840). To determine if this observation could be explained by an increased rate of A:T→G:C mutations relative to other base-pair substitutions, we developed a reversion assay to examine G:C→A:T, C:G→A:T, and A:T→G:C mutations within mouse Aprt in a Pms2 null mouse kidney cell line. The results demonstrated a 6-50-fold increase in the rate of the A:T→G:C mutations relative to the other base-pair substitutions. Additional work demonstrated that growth of the Pms2 null cells in antioxidant containing medium reduced the rate of the A:T→G:C mutations. The results are discussed with regards to the role of mismatch repair proteins in preventing base-pair substitutions, including those induced by oxidative stress.
Original language | English (US) |
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Pages (from-to) | 995-1001 |
Number of pages | 7 |
Journal | DNA Repair |
Volume | 1 |
Issue number | 12 |
DOIs | |
State | Published - Dec 5 2002 |
Keywords
- Aprt
- DNA mismatch repair
- Mammalian reversion assay
- Oxidative stress
- Pms2
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology