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- Deletion of IRC19 Causes Defects in DNA Double-Strand Break Repair Pathways in Saccharomyces cerevisiae
- Ju-Hee Choi, Oyungoo Bayarmagnai, Sung-Ho Bae
- J. Microbiol. 2024;62(9):749-758. Published online July 12, 2024
- DOI: https://doi.org/10.1007/s12275-024-00152-x
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Abstract
- DNA double-strand break (DSB) repair is a fundamental cellular process crucial for maintaining genome stability, with homologous recombination and non-homologous end joining as the primary mechanisms, and various alternative pathways such as single-strand annealing (SSA) and microhomology-mediated end joining also playing significant roles under specific conditions. IRC genes were previously identified as part of a group of genes associated with increased levels of Rad52 foci in Saccharomyces cerevisiae. In this study, we investigated the effects of IRC gene mutations on DSB repair, focusing on uncharacterized IRC10, 19, 21, 22, 23, and 24. Gene conversion (GC) assay revealed that irc10Δ, 22Δ, 23Δ, and 24Δ mutants displayed modest increases in GC frequencies, while irc19Δ and irc21Δ mutants exhibited significant reductions. Further investigation revealed that deletion mutations in URA3 were not generated in irc19Δ mutant cells following HO-induced DSBs. Additionally, irc19Δ significantly reduced frequency of SSA, and a synergistic interaction between irc19Δ and rad52Δ was observed in DSB repair via SSA. Assays to determine the choice of DSB repair pathways indicated that Irc19 is necessary for generating both GC and deletion products. Overall, these results suggest a potential role of Irc19 in DSB repair pathways, particularly in end resection process.
Review
- 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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- 7 Web of Science
- 6 Crossref
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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.
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Citations
Citations to this article as recorded by
- CSSLdb: Discovery of cancer-specific synthetic lethal interactions based on machine learning and statistic inference
Yuyang Dou, Yujie Ren, Xinmiao Zhao, Jiaming Jin, Shizheng Xiong, Lulu Luo, Xinru Xu, Xueni Yang, Jiafeng Yu, Li Guo, Tingming Liang
Computers in Biology and Medicine.2024; 170: 108066. CrossRef - ML216-Induced BLM Helicase Inhibition Sensitizes PCa Cells to the DNA-Crosslinking Agent Cisplatin
Xiao-Yan Ma, Jia-Fu Zhao, Yong Ruan, Wang-Ming Zhang, Lun-Qing Zhang, Zheng-Dong Cai, Hou-Qiang Xu
Molecules.2022; 27(24): 8790. CrossRef - Clinical significance of chromosomal integrity in gastric cancers
Rukui Zhang, Zhaorui Liu, Xusheng Chang, Yuan Gao, Huan Han, Xiaona Liu, Hui Cai, Qiqing Fu, Lei Liu, Kai Yin
The International Journal of Biological Markers.2022; 37(3): 296. CrossRef - Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms
Ji Eun Choi, Woo-Hyun Chung
Journal of Microbiology.2020; 58(2): 81. CrossRef - Genetic interactions derived from high-throughput phenotyping of 6589 yeast cell cycle mutants
Jenna E. Gallegos, Neil R. Adames, Mark F. Rogers, Pavel Kraikivski, Aubrey Ibele, Kevin Nurzynski-Loth, Eric Kudlow, T. M. Murali, John J. Tyson, Jean Peccoud
npj Systems Biology and Applications.2020;[Epub] CrossRef - DNA damage induces Yap5-dependent transcription of ECO1/CTF7 in Saccharomyces cerevisiae
Michael G. Mfarej, Robert V. Skibbens, Marco Muzi-Falconi
PLOS ONE.2020; 15(12): e0242968. CrossRef
- CSSLdb: Discovery of cancer-specific synthetic lethal interactions based on machine learning and statistic inference
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