A new role for E2F1 in DNA repair

1714 Cell Cycle volume 10 issue 11 Over the past decades it has become increasingly clear that the DnA damage response (DDR) plays a crucial role in the prevention of cancer. Our DnA is extremely vulnerable to genotoxic stress. Genotoxic insults commonly arise from within as well as from without the organism. From within, genotoxic stress can be imposed by toxic byproducts of cellular metabolism, such as reactive oxygen species. From without, genotoxic stress can be imposed by numerous chemicals as well as by irradiation, such as exposure to ionizing radiation in medical practice. The estimated number of DnA lesions is as high as 105 per cell per day.1 To ensure genomic stability, it is critical that an appropriate DnA damage response (DDR) is mounted. The DDR is a complex signaling network and involves detection of the lesion, induction of transient cell cycle arrest to allow time for and activation of repair and the execution of a cell fate decision.2 Different cell fates include resumption of cell cycle progression, induction of irreversible cell cycle arrest (cellular senescence) or induction of cell death (apoptosis). numerous factors can modulate cell fate decision, including the efficiency of DnA repair and the degree and nature of persistent lesions. DnA double-strand breaks (DsBs) are genotoxic lesions that can be induced by exposure to ionizing radiation. Activation of the threonine kinase ataxia-telangiectasia mutated (ATM) comprises a first step in the DDR to DsBs. ATM can directly phosphorylate and stabilize the tumor suppressor p53 and indirectly regulate p53 phosphorylation by activating the cell cycle regulator CHeK2.3 Components of the DDR signaling pathway are mutated in several cancers, suggesting that the DDR must be overcome during the process of tumorigenesis. Moreover, previous work has demonstrated that germline mutations Cell Cycle News & Views