Morphogenesis and the Cell Cycle

Studies of the processes leading to the construction of a bud and its separation from the mother cell in Saccharomyces cerevisiae have provided foundational paradigms for the mechanisms of polarity establishment, cytoskeletal organization, and cytokinesis. Here we review our current understanding of how these morphogenetic events occur and how they are controlled by the cell-cycle-regulatory cyclin-CDK system. In addition, defects in morphogenesis provide signals that feed back on the cyclin-CDK system, and we review what is known regarding regulation of cell-cycle progression in response to such defects, primarily acting through the kinase Swe1p. The bidirectional communication between morphogenesis and the cell cycle is crucial for successful proliferation, and its study has illuminated many elegant and often unexpected regulatory mechanisms. Despite considerable progress, however, many of the most puzzling mysteries in this field remain to be resolved.

[1]  B. Haarer,et al.  Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck , 1987, Molecular and cellular biology.

[2]  Lani Wu,et al.  Spontaneous Cell Polarization Through Actomyosin-Based Delivery of the Cdc42 GTPase , 2003, Science.

[3]  Navin Pokala,et al.  High Rates of Actin Filament Turnover in Budding Yeast and Roles for Actin in Establishment and Maintenance of Cell Polarity Revealed Using the Actin Inhibitor Latrunculin-A , 1997, The Journal of cell biology.

[4]  M. Ashe,et al.  Simultaneous yet independent regulation of actin cytoskeletal organization and translation initiation by glucose in Saccharomyces cerevisiae. , 2004, Molecular biology of the cell.

[5]  J. Pringle,et al.  Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC11 gene product and the timing of events at the budding site. , 1991, Developmental genetics.

[6]  Michael N. Hall,et al.  Cell Wall Stress Depolarizes Cell Growth via Hyperactivation of Rho1 , 1999, The Journal of cell biology.

[7]  Daniel J. Lew,et al.  A Morphogenesis Checkpoint Monitors the Actin Cytoskeleton in Yeast , 1998, The Journal of cell biology.

[8]  L. Hartwell,et al.  Genetic control of the cell-division cycle in yeast. I. Detection of mutants. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Hay-Oak Park,et al.  A GDP/GTP Exchange Factor Involved in Linking a Spatial Landmark to Cell Polarity , 2001, Science.

[10]  Anita T. Layton,et al.  Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment , 2011, Current Biology.

[11]  Hiroyuki Osada,et al.  M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Peter,et al.  Gic2p May Link Activated Cdc42p to Components Involved in Actin Polarization, Including Bni1p and Bud6p (Aip3p) , 2000, Molecular and Cellular Biology.

[13]  M. Peter,et al.  Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast. , 2000, Molecular cell.

[14]  Matthew S. Gentry,et al.  Phosphorylation-dependent regulation of septin dynamics during the cell cycle. , 2003, Developmental cell.

[15]  Angelika Amon,et al.  Mitotic CDKs control the metaphase-anaphase transition and trigger spindle elongation. , 2008, Genes & development.

[16]  Thomas Schmidt,et al.  Robust cell polarity is a dynamic state established by coupling transport and GTPase signaling , 2004, The Journal of cell biology.

[17]  Y. Ohya,et al.  Cell shape and growth of budding yeast cells in restrictive microenvironments , 2004, Yeast.

[18]  D. Lew,et al.  Nucleocytoplasmic trafficking of G2/M regulators in yeast. , 2008, Molecular biology of the cell.

[19]  Samara L. Reck-Peterson,et al.  Role of actin and Myo2p in polarized secretion and growth of Saccharomyces cerevisiae. , 2000, Molecular biology of the cell.

[20]  Chandra L. Theesfeld,et al.  Septin-Dependent Assembly of a Cell Cycle-Regulatory Module in Saccharomyces cerevisiae , 2000, Molecular and Cellular Biology.

[21]  D. Lew,et al.  Genetic Interactions among Regulators of Septin Organization , 2004, Eukaryotic Cell.

[22]  David P. Toczyski,et al.  Securin and B-cyclin/CDK are the only essential targets of the APC , 2003, Nature Cell Biology.

[23]  E. Cabib,et al.  In budding yeast, contraction of the actomyosin ring and formation of the primary septum at cytokinesis depend on each other. , 2002, Journal of cell science.

[24]  Foong May Yeong,et al.  Retention of Chs2p in the ER requires N-terminal CDK1-phosphorylation sites , 2009, Cell cycle.

[25]  Douglas I. Johnson,et al.  Saccharomyces cerevisiae Cdc42p Localizes to Cellular Membranes and Clusters at Sites of Polarized Growth , 2002, Eukaryotic Cell.

[26]  S. Reed,et al.  A cell cycle checkpoint monitors cell morphogenesis in budding yeast , 1995, The Journal of cell biology.

[27]  D. Fesquet,et al.  The budding yeast Dbf2 protein kinase localises to the centrosome and moves to the bud neck in late mitosis. , 2000, Journal of cell science.

[28]  M. Snyder,et al.  Studies concerning the temporal and genetic control of cell polarity in Saccharomyces cerevisiae , 1991, The Journal of cell biology.

[29]  U. Surana,et al.  Cdc28-Clb mitotic kinase negatively regulates bud site assembly in the budding yeast. , 2001, Journal of cell science.

[30]  Steven P. Gygi,et al.  Cdk1-Dependent Regulation of the Mitotic Inhibitor Wee1 , 2005, Cell.

[31]  Clarence S. M. Chan,et al.  The LIM domain-containing Dbm1 GTPase-activating protein is required for normal cellular morphogenesis in Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[32]  Yoshikazu Ohya,et al.  Lack of GTP-bound Rho1p in secretory vesicles of Saccharomyces cerevisiae , 2003, The Journal of cell biology.

[33]  M. Snyder,et al.  Cytoskeletal activation of a checkpoint kinase. , 2003, Molecular cell.

[34]  D. Pellman,et al.  Mechanisms for concentrating Rho1 during cytokinesis. , 2009, Genes & development.

[35]  B. Haarer,et al.  Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC3 gene product and the timing of events at the budding site , 1991, The Journal of cell biology.

[36]  Kim Nasmyth,et al.  The Polo‐like kinase Cdc5p and the WD‐repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae , 1998, The EMBO journal.

[37]  K. Labib,et al.  Inn1 couples contraction of the actomyosin ring to membrane ingression during cytokinesis in budding yeast , 2008, Nature Cell Biology.

[38]  J. Chant,et al.  An IQGAP-related protein controls actin-ring formation and cytokinesis in yeast , 1997, Current Biology.

[39]  I. Herskowitz,et al.  Localization of Bud2p, a GTPase-activating protein necessary for programming cell polarity in yeast to the presumptive bud site. , 1999, Genes & development.

[40]  David Pellman,et al.  Yeast formins regulate cell polarity by controlling the assembly of actin cables , 2002, Nature Cell Biology.

[41]  J. Chant,et al.  Establishment of cell polarity in yeast. , 1995, Cold Spring Harbor symposia on quantitative biology.

[42]  Michael Snyder,et al.  Specification of sites for polarized growth in Saccharomyces cerevisiae and the influence of external factors on site selection. , 1992, Molecular biology of the cell.

[43]  S. Reed,et al.  Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1. , 1998, Genes & development.

[44]  M. Kirschner,et al.  Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. , 1993, The EMBO journal.

[45]  E. Bi,et al.  Septin ring assembly requires concerted action of polarisome components, a PAK kinase Cla4p, and the actin cytoskeleton in Saccharomyces cerevisiae. , 2004, Molecular biology of the cell.

[46]  F. Cross,et al.  Accurate quantitation of protein expression and site-specific phosphorylation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Andrew B Goryachev,et al.  Dynamics of Cdc42 network embodies a Turing‐type mechanism of yeast cell polarity , 2008, FEBS letters.

[48]  M. Ziman,et al.  Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity , 1991, Molecular and cellular biology.

[49]  K. Kozminski,et al.  Cdc42 Interacts with the Exocyst and Regulates Polarized Secretion* , 2001, The Journal of Biological Chemistry.

[50]  D. Lew,et al.  The morphogenesis checkpoint: how yeast cells watch their figures. , 2003, Current opinion in cell biology.

[51]  S. Reed,et al.  BED1, a gene encoding a galactosyltransferase homologue, is required for polarized growth and efficient bud emergence in Saccharomyces cerevisiae , 1996, The Journal of cell biology.

[52]  J. Pringle,et al.  Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[53]  I. Herskowitz,et al.  A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator , 1997, The EMBO journal.

[54]  M. Gulli,et al.  The Cdc42p effector Gic2p is targeted for ubiquitin‐dependent degradation by the SCFGrr1 complex , 1998, The EMBO journal.

[55]  J. Pringle,et al.  Functions of microtubules in the Saccharomyces cerevisiae cell cycle , 1988, The Journal of cell biology.

[56]  I. Herskowitz,et al.  Two active states of the Ras-related Bud1/Rsr1 protein bind to different effectors to determine yeast cell polarity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Yanchang Wang,et al.  The function and regulation of budding yeast Swe1 in response to interrupted DNA synthesis. , 2006, Molecular biology of the cell.

[58]  E. Bi,et al.  Regulation of Cell Polarity by Interactions of Msb3 and Msb4 with Cdc42 and Polarisome Components , 2005, Molecular and Cellular Biology.

[59]  A. Myers,et al.  Assembly interdependence among the S. cerevisiae bud neck ring proteins Elm1p, Hsl1p and Cdc12p , 2003, Yeast.

[60]  J. Pringle,et al.  Interactions among Rax1p, Rax2p, Bud8p, and Bud9p in marking cortical sites for bipolar bud-site selection in yeast. , 2004, Molecular biology of the cell.

[61]  A. Tong,et al.  Interaction between a Ras and a Rho GTPase couples selection of a growth site to the development of cell polarity in yeast. , 2003, Molecular biology of the cell.

[62]  Chandra L. Theesfeld,et al.  Determinants of Swe1p degradation in Saccharomyces cerevisiae. , 2002, Molecular biology of the cell.

[63]  Hay-Oak Park,et al.  Specific Residues of the GDP/GTP Exchange Factor Bud5p Are Involved in Establishment of the Cell Type-specific Budding Pattern in Yeast* , 2004, Journal of Biological Chemistry.

[64]  E. Bailly,et al.  Differential cellular localization among mitotic cyclins from Saccharomyces cerevisiae: a new role for the axial budding protein Bud3 in targeting Clb2 to the mother-bud neck , 2003, Journal of Cell Science.

[65]  J. Chant,et al.  Bud10p directs axial cell polarization in budding yeast and resembles a transmembrane receptor , 1996, Current Biology.

[66]  Daniel J. Lew,et al.  Differential Susceptibility of Yeast S and M Phase CDK Complexes to Inhibitory Tyrosine Phosphorylation , 2007, Current Biology.

[67]  Rong Li,et al.  Sequential Assembly of Myosin II, an IQGAP-like Protein, and Filamentous Actin to a Ring Structure Involved in Budding Yeast Cytokinesis , 1998, The Journal of cell biology.

[68]  Jung-Eun Park,et al.  Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast , 2005, The EMBO journal.

[69]  M. Doolin,et al.  Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae , 1999, Molecular and General Genetics MGG.

[70]  M. Tyers,et al.  The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast. , 1994, Science.

[71]  Matthias Peter,et al.  Degradation of Hof1 by SCFGrr1 is important for actomyosin contraction during cytokinesis in yeast , 2005, The EMBO journal.

[72]  D. Lew,et al.  The Checkpoint Kinase Hsl1p Is Activated by Elm1p-dependent Phosphorylation , 2022 .

[73]  Eugenio Marco,et al.  Endocytosis Optimizes the Dynamic Localization of Membrane Proteins that Regulate Cortical Polarity , 2007, Cell.

[74]  Yi Zheng,et al.  Interactions among Proteins Involved in Bud-site Selection and Bud-site Assembly in Saccharomyces cerevisiae (*) , 1995, The Journal of Biological Chemistry.

[75]  Daniel J. Lew,et al.  Symmetry-Breaking Polarization Driven by a Cdc42p GEF-PAK Complex , 2008, Current Biology.

[76]  G F Sprague,et al.  Mutation of RGA1, which encodes a putative GTPase-activating protein for the polarity-establishment protein Cdc42p, activates the pheromone-response pathway in the yeast Saccharomyces cerevisiae. , 1995, Genes & development.

[77]  K. Tatchell,et al.  Role of the septin ring in the asymmetric localization of proteins at the mother-bud neck in Saccharomyces cerevisiae. , 2005, Molecular biology of the cell.

[78]  D. Botstein,et al.  Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity. , 1993, Molecular biology of the cell.

[79]  Josep Clotet,et al.  Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity , 2006, The EMBO journal.

[80]  S. Reed,et al.  Morphogenesis in the yeast cell cycle: regulation by Cdc28 and cyclins , 1993, The Journal of cell biology.

[81]  S. Gygi,et al.  Global Analysis of Cdk1 Substrate Phosphorylation Sites Provides Insights into Evolution , 2009, Science.

[82]  H. Bussey,et al.  Bud8p and Bud9p, proteins that may mark the sites for bipolar budding in yeast. , 2001, Molecular biology of the cell.

[83]  S. G. Coats,et al.  Regulation of dimorphism in Saccharomyces cerevisiae: involvement of the novel protein kinase homolog Elm1p and protein phosphatase 2A , 1993, Molecular and cellular biology.

[84]  B. Andrews,et al.  Regulation of cell polarity through phosphorylation of Bni4 by Pho85 G1 cyclin-dependent kinases in Saccharomyces cerevisiae. , 2009, Molecular biology of the cell.

[85]  Keith Burridge,et al.  Regulation of RhoGTPase crosstalk, degradation and activity by RhoGDI1 , 2010, Nature Cell Biology.

[86]  J. Thorner,et al.  Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4 , 2004, The Journal of cell biology.

[87]  David O. Morgan,et al.  Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates , 2005, Nature.

[88]  Eric L. Weiss,et al.  Mitotic Exit Control of the Saccharomyces cerevisiae Ndr/LATS Kinase Cbk1 Regulates Daughter Cell Separation after Cytokinesis , 2010, Molecular and Cellular Biology.

[89]  L. Hartwell.  Genetic control of the cell division cycle in yeast. IV. Genes controlling bud emergence and cytokinesis. , 1971, Experimental cell research.

[90]  Daniel Figeys,et al.  Activation of the Cdc42p GTPase by cyclin‐dependent protein kinases in budding yeast , 2007, The EMBO journal.

[91]  L. Hartwell.  Saccharomyces cerevisiae cell cycle. , 1974, Bacteriological reviews.

[92]  Brian D. Slaughter,et al.  Dual modes of cdc42 recycling fine-tune polarized morphogenesis. , 2009, Developmental cell.

[93]  J. Pringle,et al.  Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[94]  John J. Tyson,et al.  Mathematical model of the morphogenesis checkpoint in budding yeast , 2003, The Journal of cell biology.

[95]  Matthias Peter,et al.  Nuclear sequestration of the exchange factor Cdc24 by Far1 regulates cell polarity during yeast mating , 2000, Nature Cell Biology.

[96]  J. Chant,et al.  A mechanism of Bud1p GTPase action suggested by mutational analysis and immunolocalization , 1996, Current Biology.

[97]  J. Boyne,et al.  IQGAP and mitotic exit network (MEN) proteins are required for cytokinesis and re-polarization of the actin cytoskeleton in the budding yeast, Saccharomyces cerevisiae. , 2006, European journal of cell biology.

[98]  Richard D Kolodner,et al.  An overview of Cdk1-controlled targets and processes , 2010, Cell Division.

[99]  K Nasmyth,et al.  growth and for cytokinesis in budding yeast. Ste20-like protein kinases are required for normal localization of cell , 2007 .

[100]  Indrani Bose,et al.  The Rho‐GAP Bem2p plays a GAP‐independent role in the morphogenesis checkpoint , 2002, The EMBO journal.

[101]  E. Bi,et al.  Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II , 2010, The Journal of cell biology.

[102]  Y. Zheng,et al.  Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3. , 1994, The Journal of biological chemistry.

[103]  F. Cross,et al.  Potential Regulation of Ste20 Function by the Cln1-Cdc28 and Cln2-Cdc28 Cyclin-dependent Protein Kinases* , 1998, The Journal of Biological Chemistry.

[104]  James E. Ferrell,et al.  Substrate Competition as a Source of Ultrasensitivity in the Inactivation of Wee1 , 2007, Cell.

[105]  Angelika Amon,et al.  Closing mitosis: the functions of the Cdc14 phosphatase and its regulation. , 2004, Annual review of genetics.

[106]  J. Chant,et al.  A localized GTPase exchange factor, Bud5, determines the orientation of division axes in yeast , 2001, Current Biology.

[107]  Jason Moffat,et al.  Late-G1 cyclin–CDK activity is essential for control of cell morphogenesis in budding yeast , 2004, Nature Cell Biology.

[108]  Roger Brent,et al.  Yeast Cbk1 and Mob2 Activate Daughter-Specific Genetic Programs to Induce Asymmetric Cell Fates , 2001, Cell.

[109]  Scott A. Gerber,et al.  Multisite Phosphorylation of the Guanine Nucleotide Exchange Factor Cdc24 during Yeast Cell Polarization , 2009, PloS one.

[110]  David Y. Thomas,et al.  Cell Cycle- and Cln2p-Cdc28p-dependent Phosphorylation of the Yeast Ste20p Protein Kinase* , 1998, The Journal of Biological Chemistry.

[111]  Anthony Bretscher,et al.  Stable and dynamic axes of polarity use distinct formin isoforms in budding yeast. , 2004, Molecular biology of the cell.

[112]  F. Cross,et al.  DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae , 1988, Molecular and cellular biology.

[113]  B. Drees,et al.  Identification and functional analysis of the essential and regulatory light chains of the only type II myosin Myo1p in Saccharomyces cerevisiae , 2004, The Journal of cell biology.

[114]  S. Kron,et al.  Enhanced cell polarity in mutants of the budding yeast cyclin-dependent kinase Cdc28p. , 2001, Molecular biology of the cell.

[115]  Guang-Chao Chen,et al.  Rho1p, a Yeast Protein at the Interface Between Cell Polarization and Morphogenesis , 1996, Science.

[116]  W. Dunphy,et al.  The decision to enter mitosis. , 1994, Trends in cell biology.

[117]  R. Dominguez,et al.  Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3* , 2010, The Journal of Biological Chemistry.

[118]  K. Shokat,et al.  Targets of the cyclin-dependent kinase Cdk1 , 2003, Nature.

[119]  A. Bretscher,et al.  Mechanisms of polarized growth and organelle segregation in yeast. , 2004, Annual review of cell and developmental biology.

[120]  B. Haarer,et al.  Role of a Cdc42p effector pathway in recruitment of the yeast septins to the presumptive bud site. , 2005, Molecular biology of the cell.

[121]  Matthias Peter,et al.  Phosphorylation of Bem2p and Bem3p may contribute to local activation of Cdc42p at bud emergence , 2007, The EMBO journal.

[122]  Timothy R Hughes,et al.  RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. , 2003, Molecular biology of the cell.

[123]  P. Robbins,et al.  Chitinase is required for cell separation during growth of Saccharomyces cerevisiae. , 1991, The Journal of biological chemistry.

[124]  J. Moskow,et al.  Assembly of Scaffold-mediated Complexes Containing Cdc42p, the Exchange Factor Cdc24p, and the Effector Cla4p Required for Cell Cycle-regulated Phosphorylation of Cdc24p* , 2001, The Journal of Biological Chemistry.

[125]  T. Mitchison,et al.  Structural insights into yeast septin organization from polarized fluorescence microscopy , 2006, Nature.

[126]  P. Janmey,et al.  Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids , 2010, Cell.

[127]  T. Coleman,et al.  Negative regulation of the weel protein kinase by direct action of the nim1/cdr1 mitotic inducer , 1993, Cell.

[128]  D. Amberg,et al.  Three-dimensional imaging of the yeast actin cytoskeleton through the budding cell cycle. , 1998, Molecular biology of the cell.

[129]  Eric L. Weiss,et al.  Mitotic Exit and Separation of Mother and Daughter Cells , 2012, Genetics.

[130]  B. Daignan-Fornier,et al.  Polarized Growth in the Absence of F-Actin in Saccharomyces cerevisiae Exiting Quiescence , 2008, PloS one.

[131]  M. Polymenis,et al.  Bem1p, a scaffold signaling protein, mediates cyclin-dependent control of vacuolar homeostasis in Saccharomyces cerevisiae. , 2005, Genes & development.

[132]  M. Snyder,et al.  Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast. , 2000, Molecular cell.

[133]  D. Lew,et al.  Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast. , 1996, Molecular biology of the cell.

[134]  Rong Li,et al.  A myosin light chain mediates the localization of the budding yeast IQGAP-like protein during contractile ring formation , 2000, Current Biology.

[135]  Lynn VerPlank,et al.  Cell cycle-regulated trafficking of Chs2 controls actomyosin ring stability during cytokinesis. , 2005, Molecular biology of the cell.

[136]  F. Cross,et al.  Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. , 1993, The EMBO journal.

[137]  Jung-Eun Park,et al.  Coupling morphogenesis to mitotic entry , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[138]  Marcus B. Smolka,et al.  Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae , 2006, The Journal of cell biology.

[139]  E. Bi,et al.  Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae , 2009, The Journal of cell biology.

[140]  S. Reed,et al.  Phosphorylation of the Septin Cdc3 in G1 by the Cdc28 Kinase Is Essential for Efficient Septin Ring Disassembly , 2002, Cell cycle.

[141]  F. M. Yeong,et al.  MEN, destruction and separation: mechanistic links between mitotic exit and cytokinesis in budding yeast. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[142]  F. M. Yeong,et al.  Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother–daughter neck via the secretory pathway in budding yeast , 2006, Journal of Cell Biology.

[143]  E. O’Shea,et al.  Combining chemical genetics and proteomics to identify protein kinase substrates. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[144]  Douglas R. Kellogg,et al.  Conservation of Mechanisms Controlling Entry into Mitosis Budding Yeast Wee1 Delays Entry into Mitosis and Is Required for Cell Size Control , 2003, Current Biology.

[145]  A. Myers,et al.  Control of Saccharomyces cerevisiaeFilamentous Growth by Cyclin-Dependent Kinase Cdc28 , 1999, Molecular and Cellular Biology.

[146]  F. M. Yeong,et al.  Inactivation of mitotic kinase triggers translocation of MEN components to mother-daughter neck in yeast. , 2003, Molecular biology of the cell.

[147]  J. Caviston,et al.  The role of Cdc42p GTPase-activating proteins in assembly of the septin ring in yeast. , 2003, Molecular biology of the cell.

[148]  John R. Pringle,et al.  Bni1p, a Yeast Formin Linking Cdc42p and the Actin Cytoskeleton During Polarized Morphogenesis , 1997, Science.

[149]  Douglas R. Kellogg,et al.  Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1 , 2008, The Journal of cell biology.

[150]  Chandra L. Theesfeld,et al.  A monitor for bud emergence in the yeast morphogenesis checkpoint. , 2003, Molecular biology of the cell.

[151]  E. Bi,et al.  Initial Polarized Bud Growth by Endocytic Recycling in the Absence of Actin Cable–dependent Vesicle Transport in Yeast , 2010, Molecular biology of the cell.

[152]  M. Gustin,et al.  Osmotic stress and the yeast cytoskeleton: phenotype-specific suppression of an actin mutation , 1992, The Journal of cell biology.

[153]  S. H. Lillie,et al.  Immunofluorescence localization of the unconventional myosin, Myo2p, and the putative kinesin-related protein, Smy1p, to the same regions of polarized growth in Saccharomyces cerevisiae , 1994, The Journal of cell biology.

[154]  David G. Drubin,et al.  A Pathway for Association of Receptors, Adaptors, and Actin during Endocytic Internalization , 2003, Cell.

[155]  J. Chant,et al.  Cyk3, a novel SH3-domain protein, affects cytokinesis in yeast , 2000, Current Biology.

[156]  M. Snyder,et al.  Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. , 1999, Genes & development.

[157]  Patrick Brennwald,et al.  The Exo70 Subunit of the Exocyst Is an Effector for Both Cdc42 and Rho3 Function in Polarized Exocytosis , 2010, Molecular biology of the cell.

[158]  J. Caviston,et al.  Roles of Hof1p, Bni1p, Bnr1p, and myo1p in cytokinesis in Saccharomyces cerevisiae. , 2000, Molecular biology of the cell.

[159]  T. Höfken,et al.  The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms. , 2008, Molecular biology of the cell.

[160]  J. Ferrell,et al.  Multisite M-Phase Phosphorylation of Xenopus Wee1A , 2005, Molecular and Cellular Biology.

[161]  Yoshikazu Ohya,et al.  Polo-Like Kinase Cdc5 Controls the Local Activation of Rho1 to Promote Cytokinesis , 2006, Science.

[162]  Chandra L. Theesfeld,et al.  Opposing roles for actin in Cdc42p polarization. , 2005, Molecular biology of the cell.

[163]  U. Surana,et al.  Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28 , 1996, Molecular and cellular biology.

[164]  D. Lew,et al.  Control of Swe1p degradation by the morphogenesis checkpoint , 1998, The EMBO journal.

[165]  I. Bose,et al.  Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p , 2002, The Journal of cell biology.

[166]  Paul G. Young,et al.  Phosphorylation and inactivation of the mitotic inhibitor Weel by the nim1/cdr1 kinase , 1993, Nature.

[167]  H. Zentgraf,et al.  Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast , 2010, Journal of Cell Science.

[168]  Lynn VerPlank,et al.  Rho1 Directs Formin-Mediated Actin Ring Assembly during Budding Yeast Cytokinesis , 2002, Current Biology.

[169]  M. Kaksonen,et al.  Harnessing actin dynamics for clathrin-mediated endocytosis , 2006, Nature Reviews Molecular Cell Biology.

[170]  D. Drubin,et al.  Early-arriving Syp1p and Ede1p function in endocytic site placement and formation in budding yeast. , 2009, Molecular biology of the cell.

[171]  R. Deshaies,et al.  The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis. , 2001, Journal of cell science.

[172]  J. Thorner,et al.  Hsl7 Localizes to a Septin Ring and Serves as an Adapter in a Regulatory Pathway That Relieves Tyrosine Phosphorylation of Cdc28 Protein Kinase inSaccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[173]  C. Brenner,et al.  Yeast myosin light chain, Mlc1p, interacts with both IQGAP and class II myosin to effect cytokinesis. , 2000, Journal of cell science.

[174]  Jared L. Johnson,et al.  New Insights into How the Rho Guanine Nucleotide Dissociation Inhibitor Regulates the Interaction of Cdc42 with Membranes* , 2009, The Journal of Biological Chemistry.

[175]  V. Farkaš,et al.  Autoradiographic Study of Mannan Incorporation into the Growing Cell Walls of Saccharomyces cerevisiae , 1974, Journal of bacteriology.

[176]  M. Tyers,et al.  Regulation of cell cycle progression by Swe1p and Hog1p following hypertonic stress. , 2001, Molecular biology of the cell.

[177]  T. Pollard,et al.  Cytokinesis depends on the motor domains of myosin-II in fission yeast but not in budding yeast. , 2005, Molecular biology of the cell.

[178]  Chandra L. Theesfeld,et al.  The Morphogenesis Checkpoint in Saccharomyces cerevisiae: Cell Cycle Control of Swe1p Degradation by Hsl1p and Hsl7p , 1999, Molecular and Cellular Biology.

[179]  Charles Boone,et al.  Formins direct Arp2/3-independent actin filament assembly to polarize cell growth in yeast , 2002, Nature Cell Biology.

[180]  Thomas M. Newpher,et al.  In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin-based endocytic machinery in yeast. , 2005, Developmental cell.

[181]  J. Pringle,et al.  Identification of yeast IQGAP (Iqg1p) as an anaphase-promoting-complex substrate and its role in actomyosin-ring-independent cytokinesis. , 2007, Molecular biology of the cell.

[182]  A. Murray,et al.  S-phase feedback control in budding yeast independent of tyrosine phosphorylation of P34cdc28 , 1992, Nature.

[183]  S. Kornbluth,et al.  Cdc25 and Wee1: analogous opposites? , 2007, Cell Division.

[184]  David A. Orlando,et al.  Molecular dissection of the checkpoint kinase Hsl1p. , 2009, Molecular biology of the cell.

[185]  Curt Wittenberg,et al.  An essential G1 function for cyclin-like proteins in yeast , 1989, Cell.

[186]  Yoshimi Takai,et al.  Association of the Rho family small GTP-binding proteins with Rho GDP dissociation inhibitor (Rho GDI) in Saccharomyces cerevisiae , 1997, Oncogene.

[187]  R. Medema,et al.  The decision to enter mitosis: feedback and redundancy in the mitotic entry network , 2009, The Journal of cell biology.

[188]  Xianwen Yu,et al.  A Novel Septin-Associated Protein, Syp1p, Is Required for Normal Cell Cycle-Dependent Septin Cytoskeleton Dynamics in Yeast , 2008, Genetics.

[189]  J. Jiménez,et al.  Sep7 is essential to modify septin ring dynamics and inhibit cell separation during Candida albicans hyphal growth. , 2008, Molecular biology of the cell.

[190]  H. Wang,et al.  A checkpoint that monitors cytokinesis in Schizosaccharomyces pombe. , 2000, Journal of cell science.

[191]  E. Rubenstein,et al.  Mechanisms Regulating the Protein Kinases of Saccharomyces cerevisiae , 2007, Eukaryotic Cell.

[192]  Daniel J. Lew,et al.  Involvement of an Actomyosin Contractile Ring in Saccharomyces cerevisiae Cytokinesis , 1998, The Journal of cell biology.

[193]  Mike Tyers,et al.  Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins , 1993, Cell.

[194]  Hiroyuki Osada,et al.  Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[195]  E. Bi,et al.  Cell Polarization and Cytokinesis in Budding Yeast , 2012, Genetics.

[196]  E. Cabib,et al.  The septation apparatus, an autonomous system in budding yeast. , 2002, Molecular biology of the cell.

[197]  K. Tanaka,et al.  Molecular cloning and characterization of yeast rho GDP dissociation inhibitor. , 1994, The Journal of biological chemistry.

[198]  Gregory R. Smith,et al.  GTPase-Activating Proteins for Cdc42 , 2002, Eukaryotic Cell.

[199]  G. Tokiwa,et al.  The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. , 1988, The EMBO journal.

[200]  Christopher Minkyu Kang,et al.  Induction of S. cerevisiae filamentous differentiation by slowed DNA synthesis involves Mec1, Rad53 and Swe1 checkpoint proteins. , 2003, Molecular biology of the cell.

[201]  K. B. Shannon,et al.  The multiple roles of Cyk1p in the assembly and function of the actomyosin ring in budding yeast. , 1999, Molecular biology of the cell.

[202]  Y. Ohya,et al.  A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint , 2001, Nature Cell Biology.

[203]  J. Pringle,et al.  Roles of the CDC24 gene product in cellular morphogenesis during the Saccharomyces cerevisiae cell cycle , 1981, The Journal of cell biology.

[204]  R. Philp,et al.  Cyclin-dependent kinases control septin phosphorylation in Candida albicans hyphal development. , 2007, Developmental cell.

[205]  K. Kozminski,et al.  Transbilayer phospholipid flipping regulates Cdc42p signaling during polarized cell growth via Rga GTPase-activating proteins. , 2007, Developmental cell.

[206]  David E. Levin,et al.  Cell Wall Integrity Signaling in Saccharomyces cerevisiae , 2005, Microbiology and Molecular Biology Reviews.

[207]  Amy S. Gladfelter,et al.  Scaffold-mediated symmetry breaking by Cdc42p , 2003, Nature Cell Biology.

[208]  Daniel J. Lew,et al.  Swe1p Responds to Cytoskeletal Perturbation, Not Bud Size, in S. cerevisiae , 2005, Current Biology.

[209]  L. Hartwell,et al.  Checkpoints: controls that ensure the order of cell cycle events. , 1989, Science.

[210]  Steven P. Gygi,et al.  Cdk1 coordinates cell-surface growth with the cell cycle , 2007, Nature Cell Biology.

[211]  Indrani Bose,et al.  Singularity in Polarization: Rewiring Yeast Cells to Make Two Buds , 2009, Cell.

[212]  Paul Nurse,et al.  A spatial gradient coordinates cell size and mitotic entry in fission yeast , 2009, Nature.

[213]  Joan E. Adamo,et al.  Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud , 2001, The Journal of cell biology.

[214]  Amy S. Gladfelter,et al.  Interplay between septin organization, cell cycle and cell shape in yeast , 2005, Journal of Cell Science.

[215]  M. Solomon,et al.  Hsl1p, a Swe1p Inhibitor, Is Degraded via the Anaphase-Promoting Complex , 2000, Molecular and Cellular Biology.

[216]  Chao Zhang,et al.  The Saccharomyces cerevisiae Mob2p–Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell–specific localization of Ace2p transcription factor , 2002, The Journal of cell biology.

[217]  J. Pringle,et al.  CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae , 1990, The Journal of cell biology.

[218]  M. Crouzet,et al.  Functional characterization of the Bag7, Lrg1 and Rgd2 RhoGAP proteins from Saccharomyces cerevisiae , 2001, FEBS letters.

[219]  Christopher G. Burd,et al.  The GAP activity of Msb3p and Msb4p for the Rab GTPase Sec4p is required for efficient exocytosis and actin organization , 2003, The Journal of cell biology.

[220]  S. Gygi,et al.  The Septins Function in G1 Pathways that Influence the Pattern of Cell Growth in Budding Yeast , 2008, PloS one.

[221]  R. Cerione,et al.  Biochemical comparisons of the Saccharomyces cerevisiae Bem2 and Bem3 proteins. Delineation of a limit Cdc42 GTPase-activating protein domain. , 1993, The Journal of biological chemistry.

[222]  Wei Guo,et al.  Cyclical regulation of the exocyst and cell polarity determinants for polarized cell growth. , 2005, Molecular biology of the cell.

[223]  S. Bagrodia,et al.  Pak to the future. , 1999, Trends in cell biology.

[224]  J. Thorner,et al.  Dynamic localization of the Swe1 regulator Hsl7 during the Saccharomyces cerevisiae cell cycle. , 2001, Molecular biology of the cell.

[225]  Matthias Peter,et al.  The nucleotide exchange factor Cdc24p may be regulated by auto‐inhibition , 2004, The EMBO journal.

[226]  M. Latterich,et al.  Phosphorylation and spindle pole body localization of the Cdc15p mitotic regulatory protein kinase in budding yeast , 2000, Current Biology.

[227]  D. Hirata,et al.  Effect of Ethanol on Cell Growth of Budding Yeast: Genes That Are Important for Cell Growth in the Presence of Ethanol , 2004, Bioscience, biotechnology, and biochemistry.

[228]  Hay-Oak Park,et al.  Localization of the Rsr1/Bud1 GTPase Involved in Selection of a Proper Growth Site in Yeast* 210 , 2002, The Journal of Biological Chemistry.

[229]  T. Giddings,et al.  Saccharomyces cerevisiae Mob1p Is Required for Cytokinesis and Mitotic Exit , 2001, Molecular and Cellular Biology.

[230]  J. Moskow,et al.  Isolation and characterization of effector-loop mutants of CDC42 in yeast. , 2001, Molecular biology of the cell.

[231]  Kevan M. Shokat,et al.  Chemical genetic analysis of the budding-yeast p21-activated kinase Cla4p , 2000, Nature Cell Biology.

[232]  Norman Pavelka,et al.  Aneuploidy Underlies Rapid Adaptive Evolution of Yeast Cells Deprived of a Conserved Cytokinesis Motor , 2008, Cell.

[233]  K. Nasmyth,et al.  Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae , 1992, Nature.

[234]  R. Schekman,et al.  Differential trafficking and timed localization of two chitin synthase proteins, Chs2p and Chs3p [published erratum appears in J Cell Biol 1996 Dec;135(6 Pt 2):1925] , 1996, The Journal of cell biology.

[235]  Aljoscha Nern,et al.  Nucleocytoplasmic Shuttling of the Cdc42p Exchange Factor Cdc24p , 2000, The Journal of cell biology.

[236]  A. M. Turing,et al.  The chemical basis of morphogenesis , 1952, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.

[237]  Shinichi Morishita,et al.  G1/S cyclin-dependent kinase regulates small GTPase Rho1p through phosphorylation of RhoGEF Tus1p in Saccharomyces cerevisiae. , 2008, Molecular biology of the cell.

[238]  M. Snyder,et al.  Selection of axial growth sites in yeast requires Axl2p, a novel plasma membrane glycoprotein. , 1996, Genes & development.

[239]  D. Lew,et al.  Eavesdropping on the cytoskeleton: progress and controversy in the yeast morphogenesis checkpoint. , 2006, Current opinion in microbiology.

[240]  T Watanabe,et al.  Identification of Yeast Rho1p GTPase as a Regulatory Subunit of 1,3-β-Glucan Synthase , 1996, Science.

[241]  M. McVey,et al.  Separation of mother and daughter cells. , 2002, Methods in enzymology.

[242]  J. Heinisch,et al.  Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck , 2009, Molecular Genetics and Genomics.

[243]  J. Pringle,et al.  The anaphase-promoting complex promotes actomyosin-ring disassembly during cytokinesis in yeast. , 2009, Molecular biology of the cell.