DNA Damage Responses: p53 Induction, Cell Cycle Perturbations, and Apoptosis (original) (raw)

1. C.E. Canman,
2. C.-Y. Chen,
3. M.-H. Lee, and
4. M.B. Kastan
5. The Johns Hopkins Oncology Center, Baltimore, Maryland 21287

Excerpt

Epidemiology studies have suggested that exposure to DNA-damaging agents contributes to the development of at least 80% of human cancers (Doll and Peto 1981). Therefore, understanding the various steps involved in controlling cellular responses to DNA-damaging agents is an important component to understanding mechanisms involved in human tumorigenesis. There are three potential outcomes for cells following exposure to DNA-damaging agents (Fig. 1): (1) The cell repairs the DNA damage in a timely fashion so that subsequent progression through the cell cycle results in normal daughter cells; (2) the cell dies, and therefore cannot go on to become a tumor cell; and (3) the damage results in permanent genetic alterations in the cell which are then passed on to subsequent daughter cells. When the appropriate combination of genetic

[Graphics Excised]. Schematic representation of significant steps in the cellular responses to DNA damage and their potential contributions to tumorigenesis. Either exogenous or...