A crucial problem in biology is the mechanism by which common and general cytoskeletal elements are recruited into a diverse and dynamic array of functionally distinct structures. Part of the problem concerns the spatial and temporal regulation over the assembly and disassembly of the cytoskeleton. In addition, structures within the cell show directed motility dependent upon the activities of specific motor proteins moving over the cytoskeletal array. Our long range goals are directed at understanding the functions of one part of the cytoskeletal array, the microtubules. Microtubules are required in all eukaryotic cells, for many cellular processes, notably the segregation of chromosomes in mitosis and meiosis and for the congression of the progenomes during fertilization. Errors in these processes can have disastrous consequences for the cell. All the microtubules in yeast are organized by a single organizing center called the spindle pole body (SPB). The SPB plays a key role in microtubule function. However, little is known about the components of the SPB or how they might be functionally regulated. To address these problems we are studying the process of nuclear fusion in yeast conjugation. Nuclear fusion is a simple microtubule dependent process akin to fertilization. As a means to identifying functional components of the SPB we will use a variety of genetic techniques to identify the genes and proteins responsible for nuclear fusion. One of the genes known to be required for nuclear fusion, KAR1, encodes and essential component of the SPB. Using a variety of genetic and biochemical approaches, we aim to identify proteins that interact with the KAR1 protein since some of these should also be components of the SPB. Nuclear fusion requires that the nuclei move together in a microtubule dependent manner. Another of the genes required for nuclear fusion, KAR3, encodes a microtubule dependent motor protein which is also of critical importance in mitosis and meiosis. By a combination of genetic and biochemical analysis we aim to understand the specific functions of KAR3 and other related motor proteins in the complex movements of the chromosomes, the spindle and the nucleus in mitosis, meiosis and nuclear fusion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037739-07
Application #
3293363
Study Section
Genetics Study Section (GEN)
Project Start
1986-12-01
Project End
1995-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Matheson, Kinnari; Parsons, Lance; Gammie, Alison (2017) Whole-Genome Sequence and Variant Analysis of W303, a Widely-Used Strain of Saccharomyces cerevisiae. G3 (Bethesda) 7:2219-2226
Smith, Jean A; Hall, Allison E; Rose, Mark D (2017) Membrane curvature directs the localization of Cdc42p to novel foci required for cell-cell fusion. J Cell Biol 216:3971-3980
Melloy, Patricia G; Rose, Mark D (2017) Influence of the bud neck on nuclear envelope fission in Saccharomyces cerevisiae. Exp Cell Res 358:390-396
Smith, Jean A; Rose, Mark D (2016) Kel1p Mediates Yeast Cell Fusion Through a Fus2p- and Cdc42p-Dependent Mechanism. Genetics 202:1421-35
Haye, Joanna E; Gammie, Alison E (2015) The Eukaryotic Mismatch Recognition Complexes Track with the Replisome during DNA Synthesis. PLoS Genet 11:e1005719
Stein, Richard A; Smith, Jean A; Rose, Mark D (2015) An Amphiphysin-Like Domain in Fus2p Is Required for Rvs161p Interaction and Cortical Localization. G3 (Bethesda) 6:337-49
Ojini, Irene; Gammie, Alison (2015) Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants. G3 (Bethesda) 5:1925-35
Kim, Junwon; Rose, Mark D (2015) Stable Pseudohyphal Growth in Budding Yeast Induced by Synergism between Septin Defects and Altered MAP-kinase Signaling. PLoS Genet 11:e1005684
Rogers, Jason V; Rose, Mark D (2014) Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae. G3 (Bethesda) 5:111-21
Rogers, Jason V; McMahon, Conor; Baryshnikova, Anastasia et al. (2014) ER-associated retrograde SNAREs and the Dsl1 complex mediate an alternative, Sey1p-independent homotypic ER fusion pathway. Mol Biol Cell 25:3401-12

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