Host: The Japan Radiation Research Society, Chairman of the 52nd Annual Meeting, Toshiteru Okubo (Radiation Effects Research Foundation)
All cells have elaborate mechanisms to maintain their genomes. DNA can be damaged by reactive metabolic byproducts and by environmental mutagens. Responding to and repairing DNA damage is crucial for cell viability and disease prevention. The DNA-damage response is a signal-transduction pathway that coordinates cell-cycle transitions, DNA replication, DNA repair and apoptosis. The major regulator of the DNA-damage response are two protein kinases, ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). Both are large kinase with significant sequence homology and target an overlapping set of substrates that promote cell-cycle arrest and DNA repair. Both are involved in damage recognition step and thus play an important role on the initiation of cell cycle checkpoint. Another key player which mediates cell cycle checkpoints is tumor suppressor gene p53. p53 is activated and stabilized by ATM and serve as a transcription factor for the downstream cell cycle regulator. p53 pathway depends on the transcrption of its downstream gene and is therefore delayed after DNA damage and its role lies in the maintenance of cell cycle checkpoint. To study the role of these damage response pathways in vivo, we have isolated Medaka mutants for these three genes. In this paper we will show the phenotype of the obtained mutants.
