Cytokinesis is a crucial step in mitotic cell division which is the basis for the growth and development of eukaryotic organisms as well as for pathological conditions such as cancer. Cytokinesis is also an important mechanism for the generation of embryonic asymmetry. Therefore, understanding the mechanism and regulation of cytokinesis is likely to have broad medical implications. In animal cells, cytokinesis is known to be dependent on an actomyosin-based contractile ring. Our long term goal is to understand the spatial and temporal regulation of contratile ring assembly and function. This knowledge could also facilitate studies of other actomyosin-dependent cellular processes, such as cell locomotion and purse-string wound healing. We have recently identified an actomyosin-based ring structure in budding yeast and demonstrated its critical function during cyokinesis. This finding provides a unique opportunity for studyinh this fundamental process using a combination of genetic, biochemical and video microscopy approaches in yeast. Specifically, Dr. Li will investigate the mechanism of actin and myosin II localization during contractile ring assembly, the regulation of actomyosin ring contraction, as well as the mechanism of ring disassembly during contraction. A second goal is to understand how cytokinesis is coordinated with anaphase spindle dynamics, because such coordination is important for the successful partitioning of genetic material to progeny cells. We have already identified several structural and signaling proteins that play crucial roles in the actomyosin ring activities, and checkpoint proteins that are likely to be important for the coordination of cytokinesis with other anaphase events. We will carry out further genetic and biochemical analysis to determine their mechanism of function. Because most of these proteins have mammalian homologs, our findings should facilitate studies of similar processes in other eukaryotic organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059964-04
Application #
6526075
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Deatherage, James F
Project Start
1999-08-01
Project End
2003-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
4
Fiscal Year
2002
Total Cost
$242,515
Indirect Cost
Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Zhu, Jin; Heinecke, Dominic; Mulla, Wahid A et al. (2015) Single-Cell Based Quantitative Assay of Chromosome Transmission Fidelity. G3 (Bethesda) 5:1043-56
Potapova, Tamara A; Unruh, Jay R; Box, Andrew C et al. (2015) Karyotyping human and mouse cells using probes from single-sorted chromosomes and open source software. Biotechniques 59:335-6, 338, 340-2 passim
Chen, Guangbo; Mulla, Wahid A; Kucharavy, Andrei et al. (2015) Targeting the adaptability of heterogeneous aneuploids. Cell 160:771-784
Mulla, Wahid; Zhu, Jin; Li, Rong (2014) Yeast: a simple model system to study complex phenomena of aneuploidy. FEMS Microbiol Rev 38:201-12
Mendes Pinto, InĂªs; Rubinstein, Boris; Li, Rong (2013) Force to divide: structural and mechanical requirements for actomyosin ring contraction. Biophys J 105:547-54
Potapova, Tamara A; Zhu, Jin; Li, Rong (2013) Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos. Cancer Metastasis Rev 32:377-89
Kaplan, Kenneth B; Li, Rong (2012) A prescription for 'stress'--the role of Hsp90 in genome stability and cellular adaptation. Trends Cell Biol 22:576-83
Mendes Pinto, Ines; Rubinstein, Boris; Kucharavy, Andrei et al. (2012) Actin depolymerization drives actomyosin ring contraction during budding yeast cytokinesis. Dev Cell 22:1247-60
Chen, Guangbo; Rubinstein, Boris; Li, Rong (2012) Whole chromosome aneuploidy: big mutations drive adaptation by phenotypic leap. Bioessays 34:893-900
Zhu, Jin; Pavelka, Norman; Bradford, William D et al. (2012) Karyotypic determinants of chromosome instability in aneuploid budding yeast. PLoS Genet 8:e1002719

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