It may be more relevant to evaluate the potential contribution of mutator mutations to the efficiency of tumorigenesis, as opposed to whether mutator mutations are necessary to explain a rate of cancer lineage birth rate equal to that of clinically observed cancer incidence.
However, because the effect of a mutation on the efficiency of mRNA splicing is often difficult to predict, many mutations that cause disease through an effect on splicing are likely to remain undiscovered.
If a mutation affects the efficiency of important cellular processes, then such 'domino' effects may spread far through the network.
In agreement with an earlier observation [25], we found that the RAS2val19 mutation decreased the efficiency of G1 arrest during nutrient depletion (Fig. 1C and D).
Notably, the P79A mutation reduced the efficiency of AO7T monoubiquitylation by UbcM2.
On the other hand, destabilization of the acceptor stem by introducing G69C or G68C substitutions resulted in higher label transfer efficiency, while a C67G mutation reduced the efficiency of label transfer.
Consistent with the data obtained in our GTP labeling experiments, we found that the S140G mutation reduced the efficiency of de novo heterodimer formation under conditions where equal amounts of S-labeled protein were analyzed.
Mutation of the Y6 to an alanine residue completely abolished the activation of an NF-κB-dependent firefly luciferase reporter gene upon transfection of human tetherin into 293 cells, whereas a Y8A mutation affected the efficiency of signaling.
The upf3-nes2, upf3-nes7, and upf3-Triple-HA alleles all cause suppression of the leu2-1, tyr7-1, and can1-100 nonsense mutations, but the efficiency of suppression was less than that of upf3-Δ1 (Table 2, (6)).The growth tests suggest that all three alleles cause partial impairment of function.
Regarding the choice and the number of gRNAs, the mutation efficiency of the CMCM system depends on the gene locus.
