The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G ₂ Arrest in Cryptococcus

Abstract

Dysregulation of the cell cycle underlies many human genetic diseases and cancers, yet numerous organisms, including microbes, also manipulate the cell cycle to generate both morphologic and genetic diversity as a natural mechanism to enhance their chances for survival. The eukaryotic pathogen Cryptococcus neoformans generates morphologically distinct polyploid titan cells critical for host adaptation and subsequent disease.

Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans

“…During mitosis, the whole genome duplicates during S phase and is governed by cell cycle regulators, while in fungi, during meiosis, ploidy duplication is accomplished via cell-cell fusion and nuclear fusion between mating partners [1,32]. Besides these two fundamental cellular processes, ploidy transitions also occur during unisexual reproduction and titan cell formation in the human fungal pathogen C. deneoformans, in which ploidy increases through putative endoreplication pathways [13,18,21,36]. To examine the mechanism(s) underlying the ploidy transition from haploid to diploid during unisexual reproduction, we identified and characterized six cell cycle-regulating genes that contribute to diploidization.…”

“…Besides these two fundamental cellular processes, ploidy transitions also occur during unisexual reproduction and titan cell formation in the human fungal pathogen C . deneoformans , in which ploidy increases through putative endoreplication pathways [ 13 , 18 , 21 , 36 ]. To examine the mechanism(s) underlying the ploidy transition from haploid to diploid during unisexual reproduction, we identified and characterized six cell cycle-regulating genes that contribute to diploidization.…”

“…Different from unisexual reproduction, ploidy increases during titan cell formation was recently shown to be modulated by CLN1 expression in C . neoformans [ 36 ]. Interestingly, the orthologous CLN1 gene (CNM00990) in C .…”

“…Periodical oscillation of B-type cyclin CLB6 in clb1-5Δ cells can drive S. cerevisiae cells to re-enter S phase without undergoing mitosis and results in polyploid cell formation [35]. In C. neoformans, it was recently shown that reduced cyclin CLN1 expression in cells arrested in G2 phase can lead to titan cell formation [36]. Thus, it is likely that concerted regulation of these cell cycle regulators in C. deneoformans contributes to diploidization during unisexual reproduction.…”

“…In C . neoformans , it was recently shown that reduced cyclin CLN1 expression in cells arrested in G2 phase can lead to titan cell formation [ 36 ]. Thus, it is likely that concerted regulation of these cell cycle regulators in C .…”