Interaction between TBP and Condensin Drives the Organization and Faithful Segregation of Mitotic Chromosomes

Mol Cell. 2015 Sep 3;59(5):755-67. doi: 10.1016/j.molcel.2015.07.007. Epub 2015 Aug 6.

Abstract

Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism*
  • Centromere / genetics
  • Centromere / metabolism
  • Chromosome Segregation
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Fungal
  • Mitosis
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Point Mutation
  • Protein Interaction Domains and Motifs
  • Protein Subunits
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • TATA-Box Binding Protein / chemistry
  • TATA-Box Binding Protein / genetics*
  • TATA-Box Binding Protein / metabolism*

Substances

  • Cell Cycle Proteins
  • Cnd2 protein, S pombe
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • Schizosaccharomyces pombe Proteins
  • TATA-Box Binding Protein
  • condensin complexes
  • RNA Polymerase III
  • Adenosine Triphosphatases

Associated data

  • GEO/GSE60273