The DNA Damage Checkpoint and Human Cancer

The ability of complex organisms to survive and proliferate requires an intact genome. Because of this need,both prokaryotes and eukaryotes have developed elaborate mechanisms that monitor the integrity of the genomeand initiate responses that are appropriate to maintain genomic stability at the organismic level. This paper discusses some of the mechanisms by which mammaliancells respond to DNA damaging agents and focuses onthose mechanisms that are defective in cancer cells. Thelong-term goal of investigators working in this field is tocharacterize these DNA damage response mechanisms,understand why and how they are inactivated in humancancer, and use this information to develop effective cancer therapies...