Traffic safety for the cell: influence of cyclin-dependent kinase activity on genomic stability |
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Authors: | Enders Greg H Maude Shannon L |
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Institution: | Department of Medicine, Gastroenterology Division, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104-6140, USA. endersgh@mail.med.upenn.edu |
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Abstract: | Genomic instability has long been considered a key factor in tumorigenesis. Recent evidence suggests that DNA damage may be widespread in early pre-neoplastic states, with deregulation of cyclin-dependent kinase (Cdk) activity a driving force. Increased Cdk activity may critically reduce licensing of origins of DNA replication, drive re-replication, or mediate overexpression of checkpoint proteins, inducing deleterious cell cycle delay. Conversely, inhibition of Cdk activity may compromise replication efficiency, expression of checkpoint proteins, or activation of DNA repair proteins. These vital functions point to the impact of Cdk activity on the stability of the genome. Insight into these pathways may improve our understanding of tumorigenesis and lead to more rational cancer therapies. |
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