Table 1. Functional AKAP12 abrogates UV-induced mutagenesis.
| Cell line | AKAP12 | Repair half time (hours) | Vehicle (Mutation frequency × 10-4) | Forskolin (Mutation frequency × 10-4) | |||
|---|---|---|---|---|---|---|---|
| Vehicle | Forskolin | − UV | + UV | − UV | + UV | ||
| HEK | Wild-type | 3.1 ± 0.9a | 1.3 ± 0.2a | n.d. | 8 ± 1a | n.d. | 2 ± 1a |
| ΔPKA | 3.3 ± 0.4a | 3.1 ± 0.6b | n.d. | 33 ± 8b | n.d. | 31 ± 9b | |
| ΔNLS | 3.7 ± 0.3a | 3.5 ± 0.4b | n.d. | 29 ± 9b | n.d. | 32 ± 11b | |
| ΔATR | 3.7 ± 0.5a | 3.8 ± 0.5b | n.d. | 27 ± 5b | n.d. | 36 ± 9b | |
| Primary Melanocyte | Wild-type | 3.8 ± 0.3a | 1.3 ± 0.3a | n.d. | 11 ± 1a | n.d. | 3 ± 1a |
| ΔPKA | 3.7 ± 0.6a | 3.8 ± 0.7b | n.d. | 37 ± 7b | n.d. | 31 ± 3b | |
| ΔNLS | 3.6 ± 0.4a | 3.6 ± 0.5b | n.d. | 27 ± 6b | n.d. | 33 ± 3b | |
| ΔATR | 3.3 ± 0.4a | 3.5 ± 0.6b | n.d. | 29 ± 4b | n.d. | 35 ± 7b | |
| A375 | Wild-type | 3.4 ± 0.6a | 1.2 ± 0.3a | n.d. | 9 ± 1a | n.d. | 3 ± 1a |
| ΔPKA | 3.9 ± 0.5a | 3.8 ± 0.4b | n.d. | 23 ± 2b | n.d. | 29 ± 2b | |
| ΔNLS | 4.1 ± 0.4a | 3.7 ± 0.5b | n.d. | 28 ± 8b | n.d. | 26 ± 2b | |
| ΔATR | 4.0 ± 0.3a | 3.8 ± 0.3b | n.d. | 26 ± 2b | n.d. | 28 ± 3b | |
| SK-Mel2 | Wild-type | 3.1 ± 0.3a | 1.1 ± 0.2a | n.d. | 9 ± 1a | n.d. | 3 ± 1a |
| ΔPKA | 3.5 ± 0.2a | 3.8 ± 0.3b | n.d. | 31 ± 9b | n.d. | 33 ± 8b | |
| ΔNLS | 3.3 ± 0.4a | 3.6 ± 0.5b | n.d. | 27 ± 3b | n.d. | 28 ± 5b | |
| ΔATR | 3.6 ± 0.3a | 3.3 ± 0.3b | n.d. | 26 ± 5b | n.d. | 25 ± 8b | |
| WM3211 | Wild-type | 3.1 ± 0.2a | 1.2 ± 0.2a | n.d. | 12 ± 1a | n.d. | 3 ± 2a |
| ΔPKA | 3.3 ± 0.5a | 3.2 ± 0.4b | n.d. | 33 ± 2b | n.d. | 27 ± 6b | |
| ΔNLS | 3.4 ± 0.3a | 3.6 ± 0.3b | n.d. | 26 ± 8b | n.d. | 33 ± 5b | |
| ΔATR | 3.5 ± 0.4a | 3.6 ± 0.4b | n.d. | 25 ± 7b | n.d. | 28 ± 3b | |
Mutation frequencies in AKAP12-CRISPR silenced HEK293 cells or in a variety of AKAP12-silenced cell lines expressing siRNA-resistant AKAP12-WT or AKAP12 mutant variants. Cells were pre-treated with forskolin (10 μM) or vehicle and mock treated or exposed to UV (20 J/m2) with either colony-forming efficiency determined 21 days after 6-TG treatment or repair of [6-4]-PP up to 9 h post-UV. Repair efficiencies are expressed as time taken in hours to repair 50% of initial damage and expressed as mean ± SEM. “a" and “b": values not sharing a common letter were significantly different for each treatment as determined by one-way ANOVA; P ≤ 0.05. Data are expressed as mean ± SEM from three independent experiments. n.d., not detected.