Subject(s)
Gene Transfer Techniques , Genetic Therapy , Animals , Clinical Trials as Topic , Data Collection , Databases, Factual , Disease Models, Animal , Follow-Up Studies , Gene Transfer Techniques/adverse effects , Gene Transfer Techniques/ethics , Gene Transfer Techniques/mortality , Gene Transfer Techniques/trends , Genetic Therapy/adverse effects , Genetic Therapy/ethics , Genetic Therapy/methods , Genetic Therapy/mortality , Genetic Therapy/trends , Genetic Vectors , Humans , Practice Guidelines as Topic , Risk Factors , United States , United States Food and Drug AdministrationABSTRACT
DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.
