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The Yeast Copper Response Is Regulated by DNA Damage

Lookup NU author(s): Kangzhen Dong, Dr Stephen Addinall, Professor David Lydall, Dr Julian Rutherford

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Abstract

Copper is an essential but potentially toxic redox active metal so that the levels and distribution of this metal are carefully regulated to ensure that it binds to the correct proteins. Previous studies of copper dependent transcription in the yeast Saccharomyces cerevisiae have focused on the response of genes to changes in the exogenous levels of copper. We now report that yeast copper genes are regulated in response to the DNA damaging agents methyl methanesulfonate (MMS) and hydroxyurea by a mechanism(s) that requires the copper responsive transcription factors Mac1 and Ace1, copper superoxide dismutase (Sod1) activity and the Rad53 checkpoint kinase. Furthermore, in copper starved yeast the response of the Rad53 pathway to MMS is compromised due to a loss of Sod1 activity consistent with the model that yeast import copper to ensure Sod1 activity and Rad53 signalling. Crucially, the Mac1 transcription factor undergoes changes in its redox state in response to changing levels of copper or MMS. This study has therefore identified a novel regulatory relationship between cellular redox, copper homeostasis and the DNA damage response in yeast.

Publication metadata

Author(s): Dong K, Addinall S, Lydall D, Rutherford JC

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Biology

Year: 2013

Volume: 33

Issue: 20

Pages: 4041-4050

Print publication date: 19/08/2013

ISSN (print): 0270-7306

ISSN (electronic): 1067-8824

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/MCB.00116-13

DOI: 10.1128/MCB.00116-13

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