Maintaining the integrity of the genome prevents cancer-causing events, like loss of heterozygosity and chromosome translocations. We have shown that the ATR (ATM and Rad3-related) protein kinase is essential for genome stability and suppresses cancer in mice. As a central and upstream regulator of a signal transduction cascade activated by stalled DNA replication, ATR may stabilize the genome by preventing stalled DNA replication forks from collapsing into double strand breaks. Since DNA replication stalling occurs in every cell cycle, failure of the ATR-mediated pathway to correctly respond to stalled DNA replication forks may be a major source of the genetic deletions and translocations that cause cancer and other age-related disorders.
ATR itself has no known DNA processing activity; therefore, ATR's ability to prevent double strand break generation in the face of stalled DNA replication is likely mediated through downstream effectors. My laboratory has set out to determine what genes are regulated by ATR, how these genes stabilize stalled DNA replication forks and how these genes cooperate to prevent cancer and premature aging.
Background
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California Institute of Technology: Postdoctoral research with David Baltimore Disrupted the ATR kinase in mice and studied the role of ATR in cell cycle checkpoints, genome stability, embryonic development and
tumorigenesis.
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Harvard University : Ph.D. in Immunology with Stuart L. Schreiber (1996) Purified, cloned and performed structure/function analysis of mTOR.
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University of California at Berkeley: B.A. in Genetics (1989)
