Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>

ABSTRACT Kinetochore clustering, frequently observed in yeasts, plays a key role in genome organization and chromosome segregation. In the absence of the metaphase plate arrangement, kinetochore clustering in yeast species is believed to facilitate timely kinetochore-microtubule interactions to achi...

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Autores principales:	Vikas Yadav, Kaustuv Sanyal
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	CENP-A LINC complex microtubule organizing center mitotic spindle Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/93a849027be847ffb7bfdb7d064dae8d
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spelling	oai:doaj.org-article:93a849027be847ffb7bfdb7d064dae8d2021-11-15T15:25:50ZSad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>10.1128/mSphere.00190-182379-5042https://doaj.org/article/93a849027be847ffb7bfdb7d064dae8d2018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00190-18https://doaj.org/toc/2379-5042ABSTRACT Kinetochore clustering, frequently observed in yeasts, plays a key role in genome organization and chromosome segregation. In the absence of the metaphase plate arrangement, kinetochore clustering in yeast species is believed to facilitate timely kinetochore-microtubule interactions to achieve bivalent attachments of chromosomes during metaphase. The factors determining the dynamics of kinetochore clustering remain largely unknown. We previously reported that kinetochores oscillate between an unclustered and a clustered state during the mitotic cell cycle in the basidiomycetous yeast Cryptococcus neoformans. Based on tubulin localization patterns, while kinetochore clustering appears to be microtubule dependent, an indirect interaction of microtubules with kinetochores is expected in C. neoformans. In this study, we sought to examine possible roles of the SUN-KASH protein complex, known to form a bridge across the nuclear envelope, in regulating kinetochore clustering in C. neoformans. We show that the SUN domain protein Sad1 localizes close to kinetochores in interphase as well as in mitotic cells. Sad1 is nonessential for viability in C. neoformans but is required for proper growth and high-fidelity chromosome segregation. Further, we demonstrate that the onset of kinetochore clustering is significantly delayed in cells lacking Sad1 compared to wild-type cells. Taken together, this study identifies a novel role of the SUN domain protein Sad1 in spatiotemporal regulation of kinetochore clustering during the mitotic cell cycle in C. neoformans. IMPORTANCE The linker of nucleoskeleton and cytoskeleton (LINC) complex is present in fungi, animals, and plants. It performs diverse functions in animals, and its role(s) have recently been explored in plants. In ascomycetous yeast species, the role of the LINC complex in spindle pole body function and telomere clustering during meiosis has been determined. However, nothing is known about the LINC complex in the fungal phylum of Basidiomycota. In this study, we identified the role of the LINC complex in kinetochore dynamics as well as in nuclear migration in a basidiomycetous yeast, Cryptococcus neoformans, a human pathogen. Unlike most other yeast species, kinetochores remain unclustered during interphase but gradually cluster during mitosis in C. neoformans. We report that the LINC complex is required for timely onset of kinetochore clustering and high-fidelity chromosome segregation in C. neoformans. Thus, our study identifies a novel factor required for kinetochore clustering during mitosis in yeast species.Vikas YadavKaustuv SanyalAmerican Society for MicrobiologyarticleCENP-ALINC complexmicrotubule organizing centermitotic spindleMicrobiologyQR1-502ENmSphere, Vol 3, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	CENP-A LINC complex microtubule organizing center mitotic spindle Microbiology QR1-502
spellingShingle	CENP-A LINC complex microtubule organizing center mitotic spindle Microbiology QR1-502 Vikas Yadav Kaustuv Sanyal Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
description	ABSTRACT Kinetochore clustering, frequently observed in yeasts, plays a key role in genome organization and chromosome segregation. In the absence of the metaphase plate arrangement, kinetochore clustering in yeast species is believed to facilitate timely kinetochore-microtubule interactions to achieve bivalent attachments of chromosomes during metaphase. The factors determining the dynamics of kinetochore clustering remain largely unknown. We previously reported that kinetochores oscillate between an unclustered and a clustered state during the mitotic cell cycle in the basidiomycetous yeast Cryptococcus neoformans. Based on tubulin localization patterns, while kinetochore clustering appears to be microtubule dependent, an indirect interaction of microtubules with kinetochores is expected in C. neoformans. In this study, we sought to examine possible roles of the SUN-KASH protein complex, known to form a bridge across the nuclear envelope, in regulating kinetochore clustering in C. neoformans. We show that the SUN domain protein Sad1 localizes close to kinetochores in interphase as well as in mitotic cells. Sad1 is nonessential for viability in C. neoformans but is required for proper growth and high-fidelity chromosome segregation. Further, we demonstrate that the onset of kinetochore clustering is significantly delayed in cells lacking Sad1 compared to wild-type cells. Taken together, this study identifies a novel role of the SUN domain protein Sad1 in spatiotemporal regulation of kinetochore clustering during the mitotic cell cycle in C. neoformans. IMPORTANCE The linker of nucleoskeleton and cytoskeleton (LINC) complex is present in fungi, animals, and plants. It performs diverse functions in animals, and its role(s) have recently been explored in plants. In ascomycetous yeast species, the role of the LINC complex in spindle pole body function and telomere clustering during meiosis has been determined. However, nothing is known about the LINC complex in the fungal phylum of Basidiomycota. In this study, we identified the role of the LINC complex in kinetochore dynamics as well as in nuclear migration in a basidiomycetous yeast, Cryptococcus neoformans, a human pathogen. Unlike most other yeast species, kinetochores remain unclustered during interphase but gradually cluster during mitosis in C. neoformans. We report that the LINC complex is required for timely onset of kinetochore clustering and high-fidelity chromosome segregation in C. neoformans. Thus, our study identifies a novel factor required for kinetochore clustering during mitosis in yeast species.
format	article
author	Vikas Yadav Kaustuv Sanyal
author_facet	Vikas Yadav Kaustuv Sanyal
author_sort	Vikas Yadav
title	Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
title_short	Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
title_full	Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
title_fullStr	Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
title_full_unstemmed	Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>
title_sort	sad1 spatiotemporally regulates kinetochore clustering to ensure high-fidelity chromosome segregation in the human fungal pathogen <italic toggle="yes">cryptococcus neoformans</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/93a849027be847ffb7bfdb7d064dae8d
work_keys_str_mv	AT vikasyadav sad1spatiotemporallyregulateskinetochoreclusteringtoensurehighfidelitychromosomesegregationinthehumanfungalpathogenitalictoggleyescryptococcusneoformansitalic AT kaustuvsanyal sad1spatiotemporallyregulateskinetochoreclusteringtoensurehighfidelitychromosomesegregationinthehumanfungalpathogenitalictoggleyescryptococcusneoformansitalic
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Sad1 Spatiotemporally Regulates Kinetochore Clustering To Ensure High-Fidelity Chromosome Segregation in the Human Fungal Pathogen <italic toggle="yes">Cryptococcus neoformans</italic>

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