Studies of cellular reproduction and differentiation are central to basic biology and should also improve understanding of important diseases such as cancer. Successful analyses of these complex processes will be most likely if they are approached in relatively simple systems, such as the unicellular eukaryote yeast, in which the full power of both classical and molecular genetic methods can be brought to bear. The proposed research will use yeast to address three distinct but interconnected problesm. First, it will attempt to resolve the """"""""gene-number paradox"""""""" (i.e., the general discrepancy between classical genetic and molecular estimates of numbers of genes) and thus enhance the utility of genetic method for the study of cellular and developmental processes. The principal approach to this problem will be the molecular analysis of a chromosome on which few genes have been identified by classical mutational analyses. Additional genes will be identified as transcribed regions on cloned segmants of the chromosome, and the reason for their """"""""invisibility"""""""" to classical analyses will be explored using Southern-blotting and DNA-mediated gene disruption. Second, the genetic control of the cell cycle will be studied; the results should also help elucidate the reasons for the gene-number paradox. New cell-cycle genes will be sought by analysis of cold-sensitive-lethal mutants that arrest at specific cell-cycle stages. Analysis of extragenic suppressors of such mutants and of similar high-temperature-sensitive mutants should reveal additional genes as well as evidence about interactions among cell-cycle genes and their products. The mutant phenotypes will be characterized to derive clues to the molecular functions of the gene products and to the functional organization of cell-cycle events. New genes and evidence about intergenic interactions will also be sought by screening recombinant-DNA libraries for genes whose overexpression can suppress mutations in other genes of interest. Third, the molecular basis of cellular morphogenesis will be explored. The genetic studies just described will focus on genes that control the morphogenetic processes of the cell cycle. In addition, such genes will be cloned. Clues to the molecular functions of the gene products will then be sought by sequencing the genes and by raising antibodies that can be used to localize the gene products in the cells. The results should illuminate the roles of cytoskeletal elements and of other machanisms both in cellular reproduction and in cellular morphogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM031006-04
Application #
3278938
Study Section
Genetics Study Section (GEN)
Project Start
1982-07-01
Project End
1991-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Onishi, Masayuki; Pringle, John R (2016) Analysis of Rho-GTPase Activity During Budding Yeast Cytokinesis. Methods Mol Biol 1369:205-18
Lee, I-Ju; Wang, Ning; Hu, Wen et al. (2014) Regulation of spindle pole body assembly and cytokinesis by the centrin-binding protein Sfi1 in fission yeast. Mol Biol Cell 25:2735-49
Onishi, Masayuki; Ko, Nolan; Nishihama, Ryuichi et al. (2013) Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during yeast cytokinesis. J Cell Biol 202:311-29
Tuo, Shanshan; Nakashima, Kenichi; Pringle, John R (2013) Role of endocytosis in localization and maintenance of the spatial markers for bud-site selection in yeast. PLoS One 8:e72123
Tuo, Shanshan; Nakashima, Kenichi; Pringle, John R (2012) Apparent defect in yeast bud-site selection due to a specific failure to splice the pre-mRNA of a regulator of cell-type-specific transcription. PLoS One 7:e47621
Pollard, Luther W; Onishi, Masayuki; Pringle, John R et al. (2012) Fission yeast Cyk3p is a transglutaminase-like protein that participates in cytokinesis and cell morphogenesis. Mol Biol Cell 23:2433-44
Wloka, Carsten; Nishihama, Ryuichi; Onishi, Masayuki et al. (2011) Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast. Biol Chem 392:813-29
Nishihama, Ryuichi; Onishi, Masayuki; Pringle, John R (2011) New insights into the phylogenetic distribution and evolutionary origins of the septins. Biol Chem 392:681-7
Wu, Jian-Qiu; Ye, Yanfang; Wang, Ning et al. (2010) Cooperation between the septins and the actomyosin ring and role of a cell-integrity pathway during cell division in fission yeast. Genetics 186:897-915
Fang, Xiaodong; Luo, Jianying; Nishihama, Ryuichi et al. (2010) Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II. J Cell Biol 191:1333-50

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