October 7, 2011

Fungus toxin gets in the way in DNA

Structural studies are providing insight to how aflatoxin – a toxin produced by fungi – contributes to cancer development.

moldy bread

Aflatoxins – carcinogenic toxins produced by fungi – contaminate food. Aflatoxin B1 has been implicated in the development of human liver cancer.

A metabolite of aflatoxin B1 reacts with DNA, forming adducts that cause mutations. To understand how different chemical forms of such adducts induce differing levels of mutations, Surajit Banerjee, research fellow Kyle Brown, Martin Egli, professor of biochemistry, and Michael Stone, professor of chemistry, examined how a DNA polymerase replicated DNAs that included different aflatoxin adducts. They obtained the first structures showing how aflatoxin B1 adducts interact with a DNA polymerase.

They report in the Aug. 17 Journal of the American Chemical Society how the ability of the polymerase to bypass aflatoxin-induced DNA damage depends upon its specific chemical form, and how this relates to the structure of the adduct within the enzyme active site. The findings could provide insight into aflatoxin’s cancer-causing mechanisms.

This research was supported by the National Cancer Institute, the Vanderbilt University Center in Molecular Toxicology, and the Vanderbilt-Ingram Cancer Center.