When chromosomes are broken, cells activate a pathway, called the DNA damage checkpoint, to signal that damage has occurred. The inactivation of this checkpoint pathway is associated with many types of cancer, especially lymphoma and leukemia. The great majority of these checkpoint genes are conserved from humans to yeast. In fact, many of these genes have human homologs implicated in tumorigenesis. This application proposes to examine the mechanism by which the checkpoint is activated by DNA damage, and subsequently inactivated if that DNA damage cannot be repaired. In addition, we will examine the targets of this pathway and explore how the modification of these molecules by the checkpoint contributes to maintaining viability upon exposure to DNA damaging agents.
Cancer is the result of uncontrolled cell division and is often initiated by mutations resulting from DNA damage. In this proposal, we outline experiments that characterize proteins responsible for regulating cell division in response to DNA damage. In doing this, we can better understand how cancers arise and the characteristics of tumors that can be used to selectively target them.
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