mGem: Cut4/Apc1 and its prion form at the cross roads of cell cycle regulation, heterochromatin organization, RNAi, stress response, and evolution.
The anaphase-promoting complex/cyclosome (APC/C) complex plays a pivotal role in cell cycle progression in eukaryotes. APC/C-mediated polyubiquitination and subsequent degradation of regulatory factors ensure sister chromatid separation during mitosis and mitotic exit. Likewise, coordination between the chromodomain protein Swi6/HP1, histone methyltransferase Clr4/Suv39, and RNAi promotes heterochromatin assembly in  Schizosaccharomyces pombe . Interestingly, Cut4/Apc1 and Cut9 subunits of APC/C regulate RNAi and interact with Swi6/HP1 and Clr4/Suv39 to promote mutual recruitment at heterochromatin.  sng2-1 , a mutant of Cut4/Apc1, can assume a prion form, designated [SNG2], with defective heterochromatin silencing. As in prions, this defect is inherited in a non-Mendelian manner, accompanied by aggregation of Cut4. Paradoxically, along with greater chromosome instability and aneuploidy-phenotypes associated with cancer, the prion form displayed enhanced stress tolerance, thereby providing a trade-off between defects in chromosome integrity and survival under stress conditions. Thus, the prion form may confer evolutionary advantage.
Sharma S, Singh J