Abstract
Studies of individuals and families with an inherited predisposition to cancer have led to the identification of genes that are involved in sensing and repair of DNA damage, cell cycle control, and cell cycle checkpoint response. The DNA in our cells is continually being damaged at high frequency by byproducts of cellular metabolisms and by environmental carcinogens. DNA damage checkpoint provides a means to coordinate two critical processes: DNA repair and cell proliferation. Loss of function of these structurally diversified genes result in the loss of growth control, cell death, or genomic instability. For example, individuals with ataxia telangiectasia, characterized by neurodegeneration and high risk for cancer, carry mutations in the key checkpoint kinase ATM (mutated in ataxia telangiectasia) gene. ATM is a master protein kinase that serves as a sensor/signal transducer in response to DNA double strand breakage.