RRC ID 47302
Author Topolski B, Jakopec V, Künzel NA, Fleig U.
Title Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and Spindle Function in Schizosaccharomyces pombe.
Journal Mol Cell Biol
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.
Volume 36(24)
Pages 3128-3140
Published 2016-12-15
DOI 10.1128/MCB.00330-16
PII MCB.00330-16
PMID 27697865
PMC PMC5126298
MeSH Chromosome Segregation Chromosomes, Fungal / genetics* Cytoskeletal Proteins / chemistry Cytoskeletal Proteins / metabolism* Inositol Phosphates / metabolism Kinetochores / metabolism Microtubules / metabolism Mitosis Protein Domains Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / metabolism* Spindle Apparatus / metabolism*
IF 3.611
Times Cited 5
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
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