Fission yeast genes which disrupt mitotic chromosome segregation when overexpressed

J P Javerzat1, G Cranston, R C Allshire

  • 1M.R.C. Human Genetics Unit, Western General Hospital, Edinburgh, UK. jpaul.javerzat@ibgc.u-bordeaux2.fr

Nucleic Acids Research
|December 1, 1996
PubMed

Insights

Researchers developed a new assay in fission yeast to find genes controlling chromosome segregation. Overexpressing known and new genes (nda3+, ubc4+, mlo2+, mlo3+) disrupted chromosome segregation, with some proving lethal.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Chromosome segregation is crucial for cell division and genetic stability.
  • Identifying genes that regulate this process is essential for understanding cell cycle control and disease.

Purpose of the Study:

  • To develop a novel interference assay in Schizosaccharomyces pombe for rapid identification and cloning of genes involved in chromosome segregation.
  • To investigate the roles of known and novel genes in maintaining chromosome transmission fidelity.

Main Methods:

  • An interference assay was established using Schizosaccharomyces pombe with an inducible promoter and a non-essential minichromosome.
  • Random S.pombe cDNAs were overexpressed to observe effects on chromosome segregation.
  • Phenotypic analysis included cell cycle arrest, chromatin distribution, and minichromosome loss rates.

Main Results:

  • Overexpression of four cDNAs (nda3+, ubc4+, mlo2+, mlo3+) led to chromosome segregation defects.
  • nda3+ (beta-tubulin) and ubc4+ (ubiquitin conjugating enzyme) overexpression caused cell cycle arrest with unsegregated chromosomes.
  • mlo2+ overexpression resulted in asymmetric nuclear chromatin distribution and increased minichromosome loss.
  • mlo3+ overexpression caused complete segregation failure at high levels but not minichromosome loss at sublethal levels.

Conclusions:

  • The study confirms beta-tubulin overexpression is lethal in S.pombe.
  • ubc4+ is implicated in regulating the metaphase-anaphase transition in fission yeast.
  • Two novel genes, mlo2+ and mlo3+, are identified as important for chromosome transmission fidelity during mitosis.

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