Cell cycle checkpoints and repair of ionizing radiation damage.
Following exposure to ionizing radiation (IR), normal cells activate a delay in any phase of the cell cycle in conjunction with DNA repair mechanisms. Cell cycle delay or arrest is a programmed response that is mutable by a variety of genetic changes. DNA repair mechanisms that are responsible for the repair of otherwise lethal IR-induced double-strand breaks (DSBs) operate in a parallel pathway. The formulation of this pathway has recently been investigated, and new information regarding several mutant cell lines that are unable to execute IR-induced DSB repair are summarized. The scid mutation and defects in Ku proteins have been characterized. Molecular readouts of the properties of IR repair have been identified, including the hyperphosphorylation of the 34 kDa subunit of replication protein A. In addition, we have identified features of the G1/S IR-induced checkpoint that can be influenced by p53 status, genetic background or the levels of cell cycle proteins. A further understanding of the players in these pathways is expected to lead to the identification of molecular markers for ionizing radiation damage. Examination of the changes in these proteins may be valuable in a clinical setting for documenting radiation exposure.
D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000235:genetics; D015415:Biomarkers; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D051716:Replication Protein A
D034961:Antigens, Nuclear; D001324:Autoantigens; D015415:Biomarkers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497167:RPA1 protein, human; D051716:Replication Protein A; C497168:Rpa1 protein, mouse; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen