Bin1 homolog hob1 supports a Rad6-Set1 pathway of transcriptional repression in fission yeast

Cell Cycle. 2007 Jul 1;6(13):1655-62. doi: 10.4161/cc.6.13.4413. Epub 2007 May 8.

Abstract

Bin1 encodes a mammalian BAR adapter protein with a nuclear anti-oncogenic function that is poorly understood. To gain functional insights, we investigated the role of the fission yeast homolog hob1+ in growth arrest and survival of cells treated with phleomycin, a DNA damaging drug. Unlike wild-type cells, hob1delta cells treated with phleomycin displayed a defective growth arrest phenotype, elongating abnormally without septation or cytokinesis and eventually losing viability. Genetic investigations suggested that the survival defect in hob1delta cells reflected a deficiency in a Rad6 pathway involving histone methyltransferase Set1 that leads to transcriptional repression. In support of this connection, transcription of telomeric and centromeric heterochromatin that is normally silenced by a Rad6/Set1-dependent mechanism was aberrantly activated in hob1delta cells. Taken together, these findings suggest that hob1+ may support a mechanism of transcriptional repression possibly relevant to the role of Bin1 in cancer suppression.

Publication types

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

MeSH terms

  • Adaptation, Biological / genetics
  • Carrier Proteins / physiology*
  • Cell Proliferation
  • Cell Survival / genetics
  • Chromatin / metabolism
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / genetics
  • Gene Silencing
  • Histone-Lysine N-Methyltransferase
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Schizosaccharomyces pombe Proteins / physiology*
  • Sequence Homology
  • Signal Transduction / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Carrier Proteins
  • Chromatin
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Rad6 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • hob1 protein, S pombe
  • Histone-Lysine N-Methyltransferase
  • Set1 protein, S pombe