Faculty

Clare Mc Gowan 
Associate Professor
Department of Molecular Biology
TSRI - 1988

Education 
Ph.D., University of Dundee, Scotland, UK, 1987

Research Focus 
Cell Cycle Control in Human Cells

Discovering the molecular mechanisms regulating cell-cycle progression is a major goal in cell biology and is essential for developing an understanding of how cell proliferation is governed in the development and treatment of human disease. We use a combination of cell biology, molecular biology and biochemistry to study DNA damage checkpoints and DNA repair proteins in human cells. We have found that the G2 checkpoint involves a cascade of phosphorylation events that prevent mitosis by inhibiting the mitotic kinase, Cdc2/Cyclin B. Some of our recent studies have focused the interaction of one of the checkpoint kinases, Cds1, with a DNA repair enzyme, Mus81, that resolves strands of duplex DNA that become crossed during replication. Our overall goal is to define critical interactions between the elements of the signal transduction pathway that prevent mitotic progression and promote repair of damaged or unreplicated DNA. The information gained from these studies is likely to provide a rational basis for the improvement of radiation and chemotherapy.

Selected References 
Chen, X.-B., Melchionna, R., Denis, C.-M., Gaillard, P.-H. L., Blasina, A., Van de Weyer, I., Boddy, M. N., Russell, P., Vialard, J., and McGowan, C. H. (2001). Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol. Cell, in press.

Lopez-Girona, A., Tanaka, K., Chen, X. B., Baber, B. A., McGowan, C. H., and Russell, P. (2001). Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast. Proc Natl Acad Sci U S A 98, 11289-94.

Tanaka, K., Boddy, M. N., Chen, X. B., McGowan, C. H., and Russell, P. (2001). Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1. Mol Cell Biol 21, 3398-404.

Melchionna, R., Chen, X. B., Blasina, A., and McGowan, C. H. (2000). Threonine 68 is required for radiation-induced phosphorylation and activation of cds1. Nat Cell Biol 2, 762-5.