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Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors.
Mol Cell Biol. 2005 Dec; 25(23):10273-85.MC

Abstract

Aerobic metabolism produces reactive oxygen species, including superoxide anions, which cause DNA damage unless removed by scavengers such as superoxide dismutases. We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1, or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to replication arrest and DNA damage in Saccharomyces cerevisiae. We also find that sod1Delta strains, and to a lesser extent lys7Delta strains, when arrested with hydroxyurea (HU) show reduced induction of the MEC1 pathway effector Rnr3p and of Hug1p. The HU sensitivity of sod1Delta and lys7Delta strains is suppressed by overexpression of TKL1, a transketolase that generates NADPH, which balances redox in the cell and is required for ribonucleotide reductase activity. Our results suggest that the MEC1 pathway in sod1Delta mutant strains is sensitive to the altered cellular redox state due to increased superoxide anions and establish a new relationship between SOD1, LYS7, and the MEC1-mediated checkpoint response to replication arrest and DNA damage in S. cerevisiae.

Authors+Show Affiliations

Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, National Naval Medical Center, Building 8, Room 5101, 8901 Wisconsin Ave., Bethesda, MD 20889-5105, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

16287844

Citation

Carter, Carole D., et al. "Loss of SOD1 and LYS7 Sensitizes Saccharomyces Cerevisiae to Hydroxyurea and DNA Damage Agents and Downregulates MEC1 Pathway Effectors." Molecular and Cellular Biology, vol. 25, no. 23, 2005, pp. 10273-85.
Carter CD, Kitchen LE, Au WC, et al. Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. Mol Cell Biol. 2005;25(23):10273-85.
Carter, C. D., Kitchen, L. E., Au, W. C., Babic, C. M., & Basrai, M. A. (2005). Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. Molecular and Cellular Biology, 25(23), 10273-85.
Carter CD, et al. Loss of SOD1 and LYS7 Sensitizes Saccharomyces Cerevisiae to Hydroxyurea and DNA Damage Agents and Downregulates MEC1 Pathway Effectors. Mol Cell Biol. 2005;25(23):10273-85. PubMed PMID: 16287844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. AU - Carter,Carole D, AU - Kitchen,Lauren E, AU - Au,Wei-Chun, AU - Babic,Christopher M, AU - Basrai,Munira A, PY - 2005/11/17/pubmed PY - 2005/12/29/medline PY - 2005/11/17/entrez SP - 10273 EP - 85 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 25 IS - 23 N2 - Aerobic metabolism produces reactive oxygen species, including superoxide anions, which cause DNA damage unless removed by scavengers such as superoxide dismutases. We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1, or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to replication arrest and DNA damage in Saccharomyces cerevisiae. We also find that sod1Delta strains, and to a lesser extent lys7Delta strains, when arrested with hydroxyurea (HU) show reduced induction of the MEC1 pathway effector Rnr3p and of Hug1p. The HU sensitivity of sod1Delta and lys7Delta strains is suppressed by overexpression of TKL1, a transketolase that generates NADPH, which balances redox in the cell and is required for ribonucleotide reductase activity. Our results suggest that the MEC1 pathway in sod1Delta mutant strains is sensitive to the altered cellular redox state due to increased superoxide anions and establish a new relationship between SOD1, LYS7, and the MEC1-mediated checkpoint response to replication arrest and DNA damage in S. cerevisiae. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/16287844/Loss_of_SOD1_and_LYS7_sensitizes_Saccharomyces_cerevisiae_to_hydroxyurea_and_DNA_damage_agents_and_downregulates_MEC1_pathway_effectors_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=16287844 DB - PRIME DP - Unbound Medicine ER -