Mechanistically, it has been difficult to differentiate between the impact of the exonuclease and helicase activities of WRN in vivo since RNAi ablates all activities, while point mutants may act as dominant negatives (Crabbe et al., 2004).
It was suggested that mutant CLOCK may act as a dominant negative protein [ 19, 22].
Interestingly, Dr. Pandolfi showed that PTEN works as a homodimer or oligomer, which explains why mutant proteins may act dominant-negatively to suppress any remaining PTEN protein function.
We propose that the aggregated form of mutant p53 may act as a sink, sequestrating the native protein into the inactive conformation through a mechanism described for a typical prionoid [ 63, 64].
The opposing expression pattern of these key branch-points genes involved in ethylene and GA metabolism during GMS mutant anther development may act as an important hormone signal-mediating response to male sterility.
The expression of CNR is reduced in the rin mutant indicating that it may act downstream of RIN-MADS and CNR is also required for RIN binding to target promoters.
There were similar reports as follows: constitutive expression of stress-responsive HSP genes was augmented in the abc- mutant, indicating that AtMBF1s may act as negative regulators of HSP in Arabidopsis thaliana seedlings [ 28].
The present study showed that Tud perinuclear accumulation failed in vasQ7, a null vas allele, underlining the critical function of Vas, and was altered in aub, mael, and krimp mutants, indicating that Tud may act downstream of all examined factors in the pathway leading to nuage formation.
Perturbation of Wnt components suppresses the seam defects associated with ceh-16 mutants, suggesting that ceh-16 may act as an upstream regulator of the Wnt pathway (Huang et al., 2009).
We postulate that residual pockets of H3K9me2 that remain in RNAi mutants (Sadaie et al, 2004) may act as nucleation sites from which, in the absence of Epe1, heterochromatin can spread.
