Cross-Talk between Carbon Metabolism and the DNA Damage Response in S. cerevisiae

Cell Reports
Kobi J Simpson-LavyMark Johnston

Abstract

Yeast cells with DNA damage avoid respiration, presumably because products of oxidative metabolism can be harmful to DNA. We show that DNA damage inhibits the activity of the Snf1 (AMP-activated) protein kinase (AMPK), which activates expression of genes required for respiration. Glucose and DNA damage upregulate SUMOylation of Snf1, catalyzed by the SUMO E3 ligase Mms21, which inhibits SNF1 activity. The DNA damage checkpoint kinases Mec1/ATR and Tel1/ATM, as well as the nutrient-sensing protein kinase A (PKA), regulate Mms21 activity toward Snf1. Mec1 and Tel1 are required for two SNF1-regulated processes-glucose sensing and ADH2 gene expression-even without exogenous genotoxic stress. Our results imply that inhibition of Snf1 by SUMOylation is a mechanism by which cells lower their respiration in response to DNA damage. This raises the possibility that activation of DNA damage checkpoint mechanisms could contribute to aerobic fermentation (Warburg effect), a hallmark of cancer cells.

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Citations

May 8, 2016·Cellular Microbiology·C BraunsdorfM Schaller
Sep 24, 2020·Biochemical Society Transactions·Roger Solé-Soler, Jordi Torres-Rosell
Nov 23, 2016·Current Genetics·Lakshmi MahendrawadaShikha Laloraya
Jan 14, 2020·Genetics and Molecular Biology·José Renato Rosa CussiolFrancisco Meirelles Bastos de Oliveira
Jan 4, 2021·Current Opinion in Cell Biology·Kobi Simpson-Lavy, Martin Kupiec

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