title: A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis.
abstract: A novel gene, designated byr4, was identified in Schizosaccharomyces pombe that affects the mitotic cell cycle and shows genetic interactions with the ras1 signaling pathways. Null alleles of byr4 cause cell cycle arrest in late mitosis and permit multiple rounds of septation. The multiple septa typically divide two nuclei, but the nuclei frequently do not stain equally with 4',6-diamidino-2-phenylindole (DAPI), suggesting that byr4 is required for proper karyokinesis. Overexpression of byr4 inhibits cytokinesis, but cell cycle progression continues leading to multinucleate cells. When byr4 is overexpressed, the early steps in the cytokinesis pathway, including formation of the medial F-actin ring, occur normally; however, the later steps in the pathway, including contraction of the F-actin ring, septation, and rearrangement of the medial F-actin following mitosis, rarely occur, byr4 shows two genetic interactions with ras1. The inhibition of cytokinesis by byr4 overexpression was exacerbated by null alleles of ras1 and scd1, suggesting a link between pathways needed for cell polarity and cytokinesis. Overexpression of byr4 also partially bypasses the need for ras1 for sporulation. The electrophoretic mobility of the byr4 protein varied in response to mutants that perturb cytokinesis and karyokinesis, suggesting interactions between byr4 and these gene products. A more rapidly migrating byr4 protein was found in cells with mutations in cdc16, which undergo repeated septation, and in cdc15, which fail to form a medial F-actin ring in mitosis. A slower migrating byr4 protein was found in cells with a mutation in the beta-tubulin gene, which arrests cells at the metaphase-anaphase transition.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
authors.forename: K
authors.initials: K
authors.lastname: Song
authors.forename: K E
authors.initials: KE
authors.lastname: Mach
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Reynolds
authors.forename: C F
authors.initials: CF
authors.lastname: Albright
mesh_terms: D000199:Actins / Q000032:analysis; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry; D016764:Cell Polarity; D004271:DNA, Fungal / Q000032:analysis; D005656:Fungal Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D016153:Genes, Suppressor / Q000235:genetics*; D018816:Genes, cdc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins; D013172:Spores, Fungal; D018631:ras Proteins / Q000235:genetics
chemical_list: D000199:Actins; C100413:Byr4 protein, S pombe; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029702:Schizosaccharomyces pombe Proteins; C089769:scd1 protein, S pombe; C492657:Ras1 protein, S pombe; D018631:ras Proteins