Bin1 homolog hob1 supports a Rad6-Set1 pathway of transcriptional repression in fission yeast.
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.
Ramalingam
Arivudainambi
A
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
Prendergast
George C
GC
D000220:Adaptation, Biological / Q000235:genetics; D002352:Carrier Proteins / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism* / Q000502:physiology*; D017385:Sequence Homology; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C522422:Rad6 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C491080:hob1 protein, S pombe; D011495:Histone-Lysine N-Methyltransferase; C472830:Set1 protein, S pombe