FIGURE 3.

DBT^L mutation results in slower PER turnover. A, onset of PER degradation in cells co-expressing DBT^L is around 3.19 ± 0.07 h (blue, n = 50 cells). The onset does not depend on the initial PER level. B, half-life of PER is independent of pre-degradation abundance and on average longer because of the DBT^L mutation. With the wild-type DBT allele, PER has a half-life of 1.20 ± 0.1 h and with DBT^L the turnover is slower with a half-life of 2.05 ± 0.12 h. Plotted here are only those DBT^L cells where PER levels dropped to ≤0.5 of their pre-degradation value. C, DBT^L mutation also leads to degradation of a smaller fraction of the available PER. While DBT destabilizes PER levels to ∼10%, DBT^L activity degrades only ∼52% (0.52 ± 0.05) of PER molecules. D, long-period mutation renders DBT slightly unstable.