Molecular Controls of Cell Cycle Progression Following DNA Damage: Roles of P53 and Ataxia-Telangiectasia Gene Products
It has been suggested that exposure to environmental DNA damaging agents contributes to the development of the vast majority of human tumors1. Therefore, an understanding of the molecular events involved in the cellular responses to such exposures should provide insights into mechanisms of human carcinogenesis. Much effort over the past 25 years has been focused on how altered nucleotide bases are removed and how the linear integrity of the DNA sequence is restored2. More recently, it has become clear that the timing of these repair processes relative to various critical cellular processes, such as DNA replication, may be important determinants for dictating the cellular consequences of the DNA damage. For example, a cell which continues to replicate its DNA prior to repairing lesions in the DNA may be more likely to result in daughter cells which have altered genetic information relative to the parental cell. It would be predicted that such altered daughter cells would be more likely to develop the genetic changes which contribute to a transformed phenotype (Figure 1).
KeywordsCell Cycle Checkpoint Ataxia Telangiectasia Nijmegen Breakage Syndrome Mdm2 Gene GADD Gene
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