Translesional Synthesis on Damaged DNA

Selected Publications

Cellular DNA damage is an initiating event in mutagenesis, carcinogenesis, and aging. My research focuses on the molecular events that occur when DNA polymerases confront DNA damage, and the mechanism by which repair enzymes excise DNA damage. I have established a novel in vitro experimental system by which base substitutions and deletions can be quantified. The mutational specificity of the oxidative-damage (8-oxoguanine), food mutagens (PhlP), hormones (estrogens), and chemical carcinogens [acetylaminofluorene, benzo(a)pyrene, and ethenodeoxycitidine] are being analyzed with respect to mechanism of translesional synthesis. Combined with in vivo mutagenesis studies, I am currently exploring the mechanism of frameshift (deletion) mutation and the nature of mutagenic hot spots.

Selected Publications

Shibutani, S., Takeshita, M., and Grollman, A.P. (1991). Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature (London) 349: 431-434.

Shibutani, S. (1993). Quantitative detection of base substitutions and deletions on chemical mutagens in vitro. Chem. Res. Toxicol. 6: 625-629.

Shibutani S. and Grollman, A.P. (1993) On the mechanism of frameshift (deletion) mutagenesis in vitro. J. Biol. Chem. 256: 11703-11710.

Shibutani, S., Margulis, L A., Geacintov, N., and Grollman, A.P. (1993). Translesional synthesis on DNA template containing a single stereoisomer of dG(+)- or dG-(-)-anti-BPDE (7,8-dibydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene). Biochemistry 32: 7531-7541 .

Shibutani, S. and Grollman, A.P. (1994). Miscoding during DNA synthesis on damaged DNA templates catalyzed by mammalian cell extracts. Cell Lett. 83: 315-322.

Shibutani, S., Suzuki, N., Terashijma, I., Sugarman, S.M., Grollman, A.P., and Pearl, M.L.Tamoxifen-DNA adducts detected in endometrium obtained from patients treated with tamoxifen. Chem. Res. Toxicol. 12, 646-653 (1999).
Laboratory of Chemical Biology