Originally published as Genetics Published Articles Ahead of Print on September 15, 2006.

Genetics, Vol. 174, 1215-1228, November 2006, Copyright © 2006
doi:10.1534/genetics.106.062042

The WTM Genes in Budding Yeast Amplify Expression of the Stress-Inducible Gene RNR3

Susannah Green Tringe1, Jason Willis, Katie L. Liberatore and Stephanie W. Ruby2

Department of Molecular Genetics and Microbiology and Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131

2 Corresponding author: Department of Molecular Genetics and Microbiology MSC08-4660, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, NM 87131-0001.
E-mail: sruby{at}unm.edu

Cellular responses to DNA damage and inhibited replication are evolutionarily conserved sets of pathways that are critical to preserving genome stability. To identify new participants in these responses, we undertook a screen for regulators that, when present on a high-copy vector, alter expression of a DNA damage-inducible RNR3-lacZ reporter construct in Saccharomyces cerevisiae. From this screen we isolated a plasmid encoding two closely related paralogs, WTM1 and WTM2, that greatly increases constitutive expression of RNR3-lacZ. Moderate overexpression of both genes together, or high-level expression of WTM2 alone from a constitutive promoter, upregulates RNR3-lacZ in the absence of DNA damage. Overexpressed, tagged Wtm2p is associated with the RNR3 promoter, indicating that this effect is likely direct. Further investigation reveals that Wtm2p and Wtm1p, previously described as regulators of meiotic gene expression and transcriptional silencing, amplify transcriptional induction of RNR3 in response to replication stress and modulate expression of genes encoding other RNR subunits.