Global response of Saccharomyces cerevisiae to an alkylating agent

Global response of Saccharomyces cerevisiae to an alkylating agent

Scott A. Jelinsky and
Leona D. Samson*

Department of Cancer Cell Biology, Division of Toxicology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115

Edited by David Botstein, Stanford University School of Medicine, Stanford, CA, and approved December 7, 1998 (received for review September 16, 1998)

Abstract

DNA chip technology enables simultaneous examination of how ≈6,200 Saccharomyces cerevisiae gene transcript levels, representing the entire genome, respond to environmental change. By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, ≈325 gene transcript levels are increased and ≈76 are decreased. Of the 21 genes that already were known to be induced by a DNA-damaging agent, 18 can be scored as inducible in this data set, and surprisingly, most of the newly identified inducible genes are induced even more strongly than these 18. We examined 42 responsive and 8 nonresponsive ORFs by conventional Northern blotting, and 48 of these 50 ORFs responded as they did by DNA chip analysis, with magnitudes displaying a correlation coefficient of 0.79. Responsive genes fall into several expected and many unexpected categories. Evidence for the induction of a program to eliminate and replace alkylated proteins is presented.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: lsamson{at}sph.harvard.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

MMS,

methyl methanesulfonate;

SSPE-T,

sodium chloride/sodium phosphate/EDTA/Triton