Progression of the cell cycle is tightly regulated in order to ensure that genetic integrity is maintained and genetic information is passed correctly to daughter cells. Extensive research over the past two decades has revealed the existence of important surveillance mechanisms (referred to as checkpoints) that regulate cell cycle progression. These checkpoints monitor specific cell cycle?related processes and block cell cycle progression until these processes are completed with high fidelity. Cancer results from damage to multiple genes controlling cell division or cell death. An underlying genetic instability is required for the generation of multiple lesions that are characteristic of cancer. Genetic instability could be manifested as alterations in chromosome number as well as translocations, deletions, and insertions. Aneuploidy is frequently present in many types of tumor cell. A loss of the spindle checkpoint function and the control of anaphase entry appear to be causes leading to gross aneuploidy, a condition from which cells with an advantage for tumor growth will be selected. Thus, studying the mechanism underlying cohesion of sister chromatids and centrioles has the potential for identifying new targets for rational designing of anti-cancer drugs. In addition, a better understanding of biochemical pathways controlling checkpoint-induced programmed cell death may help us to better therapeutically induce resistant tumor cells to undergo apoptosis. We have been studying the function of molecular components in cell cycle regulation and in suppression tumorigenesis. Our recent studies on the function of Plk1, BubR1, and Sgo1 reveal that these cell cycle checkpoint regulators play an important role in the maintenance of genomic stability and suppression of tumor formation. We have obtained a series of mice with ablation of checkpoint genes. We believe these mice will be excellent animal models with which the effect of environmental agents on cacinogenesis can be studied.
Professor, Department of Environmental Medicine
Professor, Department of Biochemistry and Molecular Pharmacology
PhD from Purdue University
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