Reference - PMID:27697865 - Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and Spindle Function in Schizosaccharomyces pombe.
Reference summary
- PubMed ID
- PMID:27697865
- Title
- Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and Spindle Function in Schizosaccharomyces pombe.
- Authors
- Topolski B, Jakopec V, Künzel NA, Fleig U
- Citation
- Mol Cell Biol 2016 Dec 15;36(24):3128-3140
- Publication year
- 2016
- Abstract
- Chromosome transmission fidelity during mitosis is of critical importance for the fitness of an organism, as mistakes will lead to aneuploidy, which has a causative role in numerous severe diseases. Proper segregation of chromosomes depends on interdependent processes at the microtubule-kinetochore interface and the spindle assembly checkpoint. Here we report the discovery of a new element essential for chromosome transmission fidelity that implicates inositol pyrophosphates (IPPs) as playing a key role in this process. The protein is Asp1, the Schizosaccharomyces pombe member of the highly conserved Vip1 family. Vip1 enzymes are bifunctional: they consist of an IPP-generating kinase domain and a pyrophosphatase domain that uses such IPPs as substrates. We show that Asp1 kinase function is required for bipolar spindle formation. The absence of Asp1-generated IPPs resulted in errors in sister chromatid biorientation, a prolonged checkpoint-controlled delay of anaphase onset, and chromosome missegregation. Remarkably, expression of Asp1 variants that generated higher-than-wild-type levels of IPPs led to a faster-than-wild-type entry into anaphase A without an increase in chromosome missegregation. In fact, the chromosome transmission fidelity of a nonessential chromosome was enhanced with increased cellular IPPs. Thus, we identified an element that optimized the wild-type chromosome transmission process.
