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Kai-Ming Chou, Ph.D.
Assistant Professor Postdoctoral Studies: Yale University Ph.D., Cellular and Molecular Biology – University of Vermont |
The mechanisms that induce DNA damage and mechanisms that repair DNA are not fully understood. The particular focus of research in our laboratory is the role of apurinergic/apyrimidinic exonucleases in DNA repair. We recently identified APE1, a novel form of this enzyme in human cells, and are now investigating its properties and regulation. Our studies have the potential for therapeutic intervention in cancers caused by mutation of exonucleases.
We also examine the mechanism of DNA damage by various xenobiotics. We have identified naturally occurring compounds that inhibit APE1 which can increase the potential for mutation within DNA. A better understanding of the molecular basis of exonuclease inhibition by these compounds may be critical to a better understanding of certain cancers.
Representative Publications.
Morrical
S, Hempstead K, Morrical M, Chou KM, Ando R, Grigorieva O., Mechanisms of
assembly of the enzyme-ssDNA complexes required for
recombination-dependent DNA synthesis and repair in bacteriophage T4., Ann
N Y Acad Sci. 726:349-50, 1994.
Yassa
DS, Chou KM, Morrical SW., Characterization of an amino-terminal fragment
of the bacteriophage T4 UvsY recombination protein, Biochimie
79:275-85, 1997.
Chou
KM, Kukhanova M, Cheng YC., A novel action of human apurinic/apyrimidinic
endonuclease: excision of L-configuration deoxyribonucleoside analogs from
the 3' termini of DNA., J Biol Chem. 275(40):31009-15, 2000.
Chou,
KM, Krapcho, A.P., Hacker, M.P., Impact of the basic amine on the
biological activity and intra-cellular distribution of an
aza-anthrapyrazole: BBR 3422, Biochemical Pharmacology 62:
1337-1343, 2001.
Chou
KM, Krapcho, A.P., Horn, D.E., Hacker, M.P., The Biological
characterizations of anthracenediones and the photoaffinity analogs, Biochemical
Pharmacology 63:1143-7.
Chou
KM and Cheng YC, A Novel exonucleolytic activity of human AP endonuclease
on 3’ mispaired DNA, Nature 415:655-659, 2002.
Chou
KM and Cheng YC, The exonuclease activity of human apurinic/apyrimidinic
endonuclease (APE1). Biochemical properties and inhibition by the natural
dinucleotide Gp4G, J Biol Chem. 278:18289-96 2003.