Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion

ABSTRACT Recent studies have demonstrated that aberrant sister chromatid cohesion causes genomic instability and hence is responsible for the development of a tumor. The Chl1 (chromosome loss 1) protein (homolog of human ChlRl/DDX11 helicase) plays an essential role in the proper segregation of chro...

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Autores principales:	Nidhi Khurana, Sayan Bakshi, Wahida Tabassum, Mrinal K. Bhattacharyya, Sunanda Bhattacharyya
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Chl1 Hsp90 chromosome segregation sister chromatid cohesion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/511df149110f4af99df1013a3129c01d
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spelling	oai:doaj.org-article:511df149110f4af99df1013a3129c01d2021-11-15T15:24:22ZHsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion10.1128/mSphere.00225-182379-5042https://doaj.org/article/511df149110f4af99df1013a3129c01d2018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00225-18https://doaj.org/toc/2379-5042ABSTRACT Recent studies have demonstrated that aberrant sister chromatid cohesion causes genomic instability and hence is responsible for the development of a tumor. The Chl1 (chromosome loss 1) protein (homolog of human ChlRl/DDX11 helicase) plays an essential role in the proper segregation of chromosomes during mitosis. The helicase activity of Chl1 is critical for sister chromatid cohesion. Our study demonstrates that Hsp90 interacts with Chl1 and is necessary for its stability. We observe that the Hsp90 nonfunctional condition (temperature-sensitive iG170Dhsp82 strain at restrictive temperature) induces proteasomal degradation of Chl1. We have mapped the domains of Chl1 and identified that the presence of domains II, III, and IV is essential for efficient interaction with Hsp90. We have demonstrated that Hsp90 inhibitor 17-AAG (17-allylamino-geldenamycin) causes destabilization of Chl1 protein and enhances significant disruption of sister chromatid cohesion, which is comparable to that observed under the Δchl1 condition. Our study also revealed that 17-AAG treatment causes an increased frequency of chromosome loss to a similar extent as that of the Δchl1 cells. Hsp90 functional loss has been earlier linked to aneuploidy with very poor mechanistic insight. Our result identifies Chl1 as a novel client of Hsp90, which could be further explored to gain mechanistic insight into aneuploidy. IMPORTANCE Recently, Hsp90 functional loss has been linked to aneuploidy; however, until now none of the components of sister chromatid cohesion (SCC) have been demonstrated as the putative clients of Hsp90. In this study, we have established that Chl1, the protein which is involved in maintaining sister chromatid cohesion as well as in preventing chromosome loss, is a direct client of Hsp90. Thus, with understanding of the molecular mechanism, how Hsp90 controls the cohesion machinery might reveal new insights which can be exploited further for attenuation of tumorigenesis.Nidhi KhuranaSayan BakshiWahida TabassumMrinal K. BhattacharyyaSunanda BhattacharyyaAmerican Society for MicrobiologyarticleChl1Hsp90chromosome segregationsister chromatid cohesionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chl1 Hsp90 chromosome segregation sister chromatid cohesion Microbiology QR1-502
spellingShingle	Chl1 Hsp90 chromosome segregation sister chromatid cohesion Microbiology QR1-502 Nidhi Khurana Sayan Bakshi Wahida Tabassum Mrinal K. Bhattacharyya Sunanda Bhattacharyya Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
description	ABSTRACT Recent studies have demonstrated that aberrant sister chromatid cohesion causes genomic instability and hence is responsible for the development of a tumor. The Chl1 (chromosome loss 1) protein (homolog of human ChlRl/DDX11 helicase) plays an essential role in the proper segregation of chromosomes during mitosis. The helicase activity of Chl1 is critical for sister chromatid cohesion. Our study demonstrates that Hsp90 interacts with Chl1 and is necessary for its stability. We observe that the Hsp90 nonfunctional condition (temperature-sensitive iG170Dhsp82 strain at restrictive temperature) induces proteasomal degradation of Chl1. We have mapped the domains of Chl1 and identified that the presence of domains II, III, and IV is essential for efficient interaction with Hsp90. We have demonstrated that Hsp90 inhibitor 17-AAG (17-allylamino-geldenamycin) causes destabilization of Chl1 protein and enhances significant disruption of sister chromatid cohesion, which is comparable to that observed under the Δchl1 condition. Our study also revealed that 17-AAG treatment causes an increased frequency of chromosome loss to a similar extent as that of the Δchl1 cells. Hsp90 functional loss has been earlier linked to aneuploidy with very poor mechanistic insight. Our result identifies Chl1 as a novel client of Hsp90, which could be further explored to gain mechanistic insight into aneuploidy. IMPORTANCE Recently, Hsp90 functional loss has been linked to aneuploidy; however, until now none of the components of sister chromatid cohesion (SCC) have been demonstrated as the putative clients of Hsp90. In this study, we have established that Chl1, the protein which is involved in maintaining sister chromatid cohesion as well as in preventing chromosome loss, is a direct client of Hsp90. Thus, with understanding of the molecular mechanism, how Hsp90 controls the cohesion machinery might reveal new insights which can be exploited further for attenuation of tumorigenesis.
format	article
author	Nidhi Khurana Sayan Bakshi Wahida Tabassum Mrinal K. Bhattacharyya Sunanda Bhattacharyya
author_facet	Nidhi Khurana Sayan Bakshi Wahida Tabassum Mrinal K. Bhattacharyya Sunanda Bhattacharyya
author_sort	Nidhi Khurana
title	Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
title_short	Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
title_full	Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
title_fullStr	Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
title_full_unstemmed	Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion
title_sort	hsp90 is essential for chl1-mediated chromosome segregation and sister chromatid cohesion
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/511df149110f4af99df1013a3129c01d
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Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion

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