The age-dependent increase in genomic instability is mediated by Rev1. (A) mRNA levels of REV1 in wild-type (WT; DBY746), sch9Δ, gis1Δ, and gis1Δ sch9Δ cells. mRNA extracted from 3-d-old cells were subjected to quantitative real-time PCR analysis. **, P < 0.01, mutant versus WT; ^^, P < 0.01, mutant versus sch9Δ, n = 12, ANOVA test, Tukey's test. (B) Chronological survival and (C) mutation frequency over time in the CAN1 gene of wild type, sch9Δ, rev1Δ, and rev1D sch9Δ in both the DBY746 and BY4741 genetic backgrounds. ***, P < 0.001; rev1Δ versus WT. ^, P < 0.05; rev1Δ sch9Δ versus sch9Δ, two-tailed t test at indicated time points (n = 9). (D) Chronological survival and (E) mutation frequency over time in the CAN1 gene of wild-type, sch9Δ, rev1Δ, and cells overexpressing SCH9 or REV1. *, P < 0.05; **, P < 0.01; ***, P < 0.001; mutant versus WT. ^, P < 0.05; ^^, P < 0.01; sch9Δ REV1ox versus sch9Δ. a, P < 0.05; rev1ΔSCH9ox versus SCH9ox, two-tailed t test at indicated time points (n = 6–9). (F) Chronological survival and (G) GCRs in the wild type and rev1Δ mutants. **, P < 0.01; ***, P < 0.001; rev1Δ versus WT, two-tailed t test at indicated time points (n = 4). Error bars indicate ±SEM.