- Functional Characterization of DNA N‑Glycosylase Ogg1 and Ntg1 in DNA Damage Stress of Cryptococcus neoformans
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Kwang-Woo Jung , Sunhak Kwon , Jong-Hyun Jung , Sangyong Lim , Yong-Sun Bahn
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J. Microbiol. 2023;61(11):981-992. Published online December 6, 2023
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DOI: https://doi.org/10.1007/s12275-023-00092-y
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Reactive oxygen species induce DNA strand breaks and DNA oxidation. DNA oxidation leads to DNA mismatches, resulting
in mutations in the genome if not properly repaired. Homologous recombination (HR) and non-homologous end-joining
(NHEJ) are required for DNA strand breaks, whereas the base excision repair system mainly repairs oxidized DNAs, such as
8-oxoguanine and thymine glycol, by cleaving the glycosidic bond, inserting correct nucleotides, and sealing the gap. Our
previous studies revealed that the Rad53-Bdr1 pathway mainly controls DNA strand breaks through the regulation of HRand
NHEJ-related genes. However, the functional roles of genes involved in the base excision repair system remain elusive
in Cryptococcus neoformans. In the present study, we identified OGG1 and NTG1 genes in the base excision repair system
of C. neoformans, which are involved in DNA oxidation repair. The expression of OGG1 was induced in a Hog1-dependent
manner under oxidative stress. On the other hand, the expression of NTG1 was strongly induced by DNA damage stress in a
Rad53-independent manner. We demonstrated that the deletion of NTG1, but not OGG1, resulted in elevated susceptibility
to DNA damage agents and oxidative stress inducers. Notably, the ntg1Δ mutant showed growth defects upon antifungal
drug treatment. Although deletion of OGG1 or NTG1 did not increase mutation rates, the mutation profile of each ogg1Δ
and ntg1Δ mutant was different from that of the wild-type strain. Taken together, we found that DNA N-glycosylase Ntg1
is required for oxidative DNA damage stress and antifungal drug resistance in C. neoformans.
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Citations
Citations to this article as recorded by  - Fungal DNA damage repair: from model to driver of virulence and AMR
Callum Parkin, Adam G. Bainbridge, Johannes Gregor Matthias Rack
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Qiangqiang Wang, Xiaoxuan Feng, Yurun Su, Naiwen Zhang, Yevheniia Dudnyk, Hongxuan He
Veterinary Sciences.2026; 13(8): 815. CrossRef
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