MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants
Figure 4
Methyl methanesulfonate exposure resulted in C:G→G:C transversions in mtDNA.
Fractions of different base substitutions in heterozygous strains with a wild type (WT) MIP1 allele and a mutant mip1 encoding the Q264H variant in the presence (3 mM) or absence (0 mM) of MMS. The following number of mutants was sequenced for each group: Wt (0 mM MMS), 5; Wt (3 mM MMS), 15; Q264H (0 mM MMS), 28; Q264H (0 mM MMS), 71. P-values for the C to G mutations were calculated using a one-tailed Fisher's Exact test. The p-value for the 0.46 fraction of G to C mutations with the Q264H and 3 mM MMS as compared to no MMS was <0.0001. The p-value of the 0.40 fraction of G to C mutations for the WT comparing 3 mM MMS with no MMS was 0.17 and <0.0001 using our WT no MMS data and the WT data from Kalifa and Sia [46], respectively. MMS, methyl methanesulfonate; mtDNA, mitochondrial DNA; Wt, wild type.