DNA Damage and Polyploidization英文文献.pdfVIP

Chapter 4 DNA Damage and Polyploidization Jeremy P.H. Chow and Randy Y.C. Poon* e Abstract t u growing body of evidence indicates that polyploidization triggers chromosomal instability b and contributes to tumorigenesis. DNA damage is increasingly being recognized for its i r Aroles in promoting polyploidization. Although elegant mechanisms known as the DNA t s damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that i uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the D checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. t o Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, N including lagging chromosomes, chromosomal fragments and chromosomal bridges. The pres‑ ence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that o if cytokinesis failure is coupled with defects of the p53‑dependent postmitotic checkpoint D pathway, cells can enter S phase and become polyploids. Progress in the past several years has e unraveled some of the underlying principles of these pathways and underscored the important c role of DNA dama