Transcriptional Response of Yeast to Aflatoxin B1: Recombinational Repair Involving RAD51 and RAD1

AUTOR(ES)

Keller-Seitz, Monika U.

FONTE

The American Society for Cell Biology

RESUMO

The potent carcinogen aflatoxin B1 is a weak mutagen but a strong recombinagen in Saccharomyces cerevisiae. Aflatoxin B1 exposure greatly increases frequencies of both heteroallelic recombination and chromosomal translocations. We analyzed the gene expression pattern of diploid cells exposed to aflatoxin B1 using high-density oligonucleotide arrays comprising specific probes for all 6218 open reading frames. Among 183 responsive genes, 46 are involved in either DNA repair or in control of cell growth and division. Inducible growth control genes include those in the TOR signaling pathway and SPO12, whereas PKC1 is downregulated. Eleven of the 15 inducible DNA repair genes, including RAD51, participate in recombination. Survival and translocation frequencies are reduced in the rad51 diploid after aflatoxin B1 exposure. In mec1 checkpoint mutants, aflatoxin B1 exposure does not induce RAD51 expression or increase translocation frequencies; however, when RAD51 is constitutively overexpressed in the mec1 mutant, aflatoxin B1 exposure increased translocation frequencies. Thus the transcriptional profile after aflatoxin B1 exposure may elucidate the genotoxic properties of aflatoxin B1.

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