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DNA Damage and Polyploidization

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Polyploidization and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 676))

Abstract

A growing body of evidence indicates that polyploidization triggers chromosomal instability and contributes to tumorigenesis. DNA damage is increasingly being recognized for its roles in promoting polyploidization. Although elegant mechanisms known as the DNA damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, including lagging chromosomes, chromosomal fragments and chromosomal bridges. The presence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that if cytokinesis failure is coupled with defects of the p53-dependent postmitotic checkpoint pathway, cells can enter S phase and become polyploids. Progress in the past several years has unraveled some of the underlying principles of these pathways and underscored the important role of DNA damage in polyploidization. Furthermore, polyploidization per se may also be an important determinant of sensitivity to DNA damage, thereby may offer an opportunity for novel therapies.

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  1. Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

    Jeremy P.H. Chow & Randy Y.C. Poon

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  1. Jeremy P.H. Chow
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  2. Randy Y.C. Poon
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Correspondence to Randy Y.C. Poon .

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  1. Department of Biochemistry, Hong Kong University of Science and Technology Clear Water Bay, Hong Kong, China

    Randy Y. C. Poon MA, PhD

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Chow, J.P., Poon, R.Y. (2010). DNA Damage and Polyploidization. In: Poon, R.Y.C. (eds) Polyploidization and Cancer. Advances in Experimental Medicine and Biology, vol 676. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6199-0_4

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