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Nancy C. Walworth
Professor
UMDNJ-RWJMS
Dept. of Pharmacology
Room 532
Busch Campus
Piscataway, NJ 08854
(732) 235-5661
FAX-4073
walworna@umdnj.edu
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Cell cycle checkpoint control in response
to DNA damage
Cell cycle
checkpoints ensure the integrity of the genome from one replicative cell
cycle to the next. In the event of catastrophic damage to the genome, cells of multicellular eukaryotes can undergo apoptosis, presumably to
eliminate them from the cell population and reduce the risk of
propagating genetically unstable cells. Alternatively, cells may
respond to DNA damage by undergoing a transient arrest of the cell
cycle, which correlates with their ability to survive exposure to DNA
damaging agents. This response requires the DNA damage checkpoint
pathway; if compromised by mutation or drug treatment, cells will enter
mitosis with damaged DNA and die. The fission yeast has been an
extremely valuable system for identifying and characterizing components
of the DNA damage checkpoint. Indeed, many proteins that are now known
to function in the checkpoint pathway in mammalian cells were identified
solely based on their sequence homology to proteins that were identified
genetically and functionally in yeast. Thus, it is clear that the
identification of proteins in yeast using the power of classical
genetics is a valid and productive means of identifying and gaining
insight into the function of mammalian counterparts.
My laboratory
aims to understand the mechanism through which the protein kinase Chk1
controls the DNA damage checkpoint in eukaryotic cells. Using a
combined genetic and biochemical approach, we focus much of our effort
on dissecting the molecular events that control Chk1 function and the
targets of Chk1 that regulate cell cycle progression. We have initiated
studies on Msc1, a protein found to compensate for loss of Chk1 function
that is homologous to a tumor suppressor binding protein in mammalian
cells. The Msc1 protein appears to be important for histone
modifications of chromatin for genomic stability and for survival after
DNA damage. Future directions will explore the cellular role of Msc1 in
these processes.
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