MINIREVIEW] Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy

Ji Eun Choi; Woo-Hyun Chung

doi:10.1007/s12275-019-8475-2

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MINIREVIEW] Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy: Ji Eun Choi ^1,2, Woo-Hyun Chung ^1,2; Journal of Microbiology 2019;57(1):9-17.
DOI: https://doi.org/10.1007/s12275-019-8475-2
Published online: December 29, 2018

¹College of Pharmacy, Duksung Women’s University, Seoul 01369, Republic of Korea, ²Innovative Drug Center, Duksung Women’s University, Seoul 01369, Republic of Korea¹College of Pharmacy, Duksung Women’s University, Seoul 01369, Republic of Korea, ²Innovative Drug Center, Duksung Women’s University, Seoul 01369, Republic of Korea

Corresponding author: Woo-Hyun Chung , Tel: +82-2-901-8737;,

Received: 31 August 2018 • Revised: 12 October 2018 • Accepted: 12 October 2018

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Abstract

Synthetic lethality is an extreme form of negative genetic epistasis that arises when a combination of functional deficiency in two or more genes results in cell death, whereas none of the single genetic perturbations are lethal by themselves. This unconventional genetic interaction is a modification of the concept of essentiality that can be exploited for the purpose of targeted cancer therapy. The yeast Saccharomyces cerevisiae has been pivotally used for early large-scale synthetic lethal screens due to its experimental advantages, but recent advances in gene silencing technology have now made direct high-throughput analysis possible in higher organisms. Identification of tumor-specific alterations and characterization of the mechanistic principles underlying synthetic lethal interaction are the key to applying synthetic lethality to clinical cancer treatment by enabling genome-driven oncological research. Here, we provide emerging ideas on the synthetic lethal interactions in budding yeast, particularly between cellular processes responsible for oxidative stress response and DNA damage repair, and discuss how they can be appropriately utilized for context-dependent cancer therapeutics.

Keywords: synthetic lethality;genetic interaction;oxidative stress response;DNA double-strand break repair;damage checkpoint signaling;anticancer therapy

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MINIREVIEW] Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy

J. Microbiol. 2019;57(1):9-17. Published online December 29, 2018

DOI: https://doi.org/10.1007/s12275-019-8475-2

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