Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans

Jung, Kwang‐Woo; Kwon, Sunhak; Jung, Jong‐Hyun; Bahn, Yong-Sun

doi:10.1128/spectrum.01044-22

Cited by 2 publications

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“…Our previous studies reveal that Cryptococcus YNK1 appears to be essential for growth, while the ham1 Δ mutant showed WT-levels of resistance in response to stress responses ( Jin et al., 2020 ). Supporting this, nucleotide metabolism is crucial for DNA damage stress as well as DNA replication stress ( Jung et al., 2022 ). These data indicate that Cryptococcus Lkh1 may function in response to DNA damage stress by regulating nucleotide metabolism.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence of Cryptococcus neoformans

Kwon,

Choi,

Kim

et al. 2024

Front. Cell. Infect. Microbiol.

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Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in Cryptococcus neoformans, a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a LKH1 homologous gene and constructed a strain with a deleted LKH1 and a complemented strain. Similar to other fungi, the lkh1Δ mutant showed intrinsic growth defects. We observed that C. neoformans Lkh1 was involved in diverse stress responses, including oxidative stress and cell wall stress. Particularly, Lkh1 regulates DNA damage responses in Rad53-dependent and -independent manners. Furthermore, the absence of LKH1 reduced basidiospore formation. Our observations indicate that Lkh1 becomes hyperphosphorylated upon treatment with rapamycin, a TOR protein inhibitor. Notably, LKH1 deletion led to defects in melanin synthesis and capsule formation. Furthermore, we found that the deletion of LKH1 led to the avirulence of C. neoformans in a systemic cryptococcosis murine model. Taken together, Lkh1 is required for the stress response, sexual differentiation, and virulence of C. neoformans.

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Section: Discussionmentioning

confidence: 99%

Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence of Cryptococcus neoformans

Kwon,

Choi,

Kim

et al. 2024

Front. Cell. Infect. Microbiol.

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Functional Characterization of DNA N-Glycosylase Ogg1 and Ntg1 in DNA Damage Stress of Cryptococcus neoformans

Jung,

Kwon,

Jung

et al. 2023

J Microbiol.

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Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans

Abstract: Upon DNA replication or damage stresses, it is critical to provide proper levels of deoxynucleotide triphosphates (dNTPs) and activate DNA repair machinery. Ribonucleotide reductases (RNRs), which are composed of large and small subunits, are required for synthesizing dNTP.

Cited by 2 publications

References 48 publications

Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence of Cryptococcus neoformans

Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence of Cryptococcus neoformans

Functional Characterization of DNA N-Glycosylase Ogg1 and Ntg1 in DNA Damage Stress of Cryptococcus neoformans

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