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, hob1? 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 hob1? 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 hob1? 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.