Journal of Microbiology

Reviews

Synthetic rescue in Saccharomyces cerevisiae: Concepts, large-scale genetic mapping, and functional implications: Ji Eun Choi, Woo-Hyun Chung; Received December 30, 2025 Accepted February 2, 2026 Published online March 12, 2026; DOI: https://doi.org/10.71150/jm.2512017 [Epub ahead of print]

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Abstract PDF: Synthetic rescue (SR) describes a genetic interaction in which the deleterious effect of a primary mutation is compensated by a second mutation, restoring cellular function or viability. In Saccharomyces cerevisiae, SR complements synthetic lethality (SL) by revealing compensatory mechanisms that maintain essential biological processes. Classical studies established SR as a fundamental principle of genetic robustness in yeast. Subsequent development of high-throughput genetic tools, including Synthetic Genetic Array (SGA), Epistatic Miniarray Profile (E-MAP), and CRISPR interference (CRISPRi), has enabled systematic identification of SR interactions across pathways of genome maintenance, proteostasis, and metabolism. Integration of these experimental datasets with computational and network-based analyses has transformed SR research from descriptive genetics into a predictive framework. Databases such as BioGRID, TheCellMap, and Mslar further support SR inference and link yeast genetic networks to human disease models. Understanding SR has important translational implications. The same compensatory logic that restores viability in yeast can explain therapeutic resistance in cancer cells. Together, these insights reveal SR as a powerful concept connecting microbial genetics with systems medicine, emphasizing that robustness and resilience are dynamic properties of living systems.

Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms: Ji Eun Choi , Woo-Hyun Chung; J. Microbiol. 2020;58(2):81-91. Published online December 23, 2019; DOI: https://doi.org/10.1007/s12275-020-9520-x

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The DNA damage checkpoint signaling pathway is a highly conserved surveillance mechanism that ensures genome integrity by sequential activation of protein kinase cascades. In mammals, the main pathway is orchestrated by two central sensor kinases, ATM and ATR, that are activated in response to DNA damage and DNA replication stress. Patients lacking functional ATM or ATR suffer from ataxia-telangiectasia (A-T) or Seckel syndrome, respectively, with pleiotropic degenerative phenotypes. In addition to DNA strand breaks, ATM and ATR also respond to oxidative DNA damage and reactive oxygen species (ROS), suggesting an unconventional function as regulators of intracellular redox status. Here, we summarize the multiple roles of ATM and ATR, and of their orthologs in Saccharomyces cerevisiae, Tel1 and Mec1, in DNA damage checkpoint signaling and the oxidative stress response, and discuss emerging ideas regarding the possible mechanisms underlying the elaborate crosstalk between those pathways. This review may provide new insights into the integrated cellular strategies responsible for maintaining genome stability in eukaryotes with a focus on the yeast model organism.

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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 , Woo-Hyun Chung; 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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Abstract PDF

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.

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