Faculty / Research

Masaru Takeshita, PhD

Research Professor Emeritus 

 

Ph.D., Tokyo Kyoiku University, Japan

Postdoctoral, Harvard Medical School

 

Genetic Toxicology: Molecular Biology of DNA Damage and Repair

In our laboratory, research focuses on damage to DNA generated by chemical carcinogens and antitumor agents. Based on previous work, we have proposed a model in which bleomycin containing ferrous ion binds to and cleaves duplex DNA, leading to strand scission and generation of abasic sites, the most common forms of DNA damage. Abasic sites in DNA are also generated by enzymatic and spontaneous processes. Using shuttle plasmid vectors containing synthetic abasic sites, we are investigating the mutagenesis and repair of these lesions. Mechanisms by which abasic sites are recognized and cleaved by mammalian AP endonucleases are being studied. Experimental systems have also been devised that allow us to explore the role of homologous recombination in DNA repair and in maintaining genetic instability.

Giloni, L., Takeshita, M., Johnson, F., Iden, C., and Grollman, A.P. (1981). Bleomycin-induced strand scission of DNA: mechanism of deoxyribose cleavage. J. Biol. Chem. 256: 8606-8615.

Takeshita, M., Chang, C.-N., Johnson, F., Will, S.G., and Grollman, A.P.(1987). Oligodeoxynucleotides containing synthetic abasic sites: model substrates for DNA polymerases and AP endonucieases. J. Biol. Chem. 262: 1017110179.

Takeshita, M. and Eisenberg, W. (1994). Mechanism of mutation on DNA templates containing synthetic abasic sites: study with a double-strand vector. Nucl. Acids Res. 22: 1897-1902.

Takeuchi, M,. Lillis, R., Demple, B., and Takeshita, M. (1994). Interactions of Escherichia coli endonuclease IV and exonuclease III with abasic sites in DNA. J. Biol. Chem.269: 21907-21914.