Sth1, the Key Subunit of the RSC Chromatin Remodeling Complex, Is Essential in Maintaining Chromosomal Integrity and Mediating High Fidelity Chromosome Segregation in the Human Fungal Pathogen Candida albicans

Priya Prasad,Kaustuv Sanyal,Santanu K Ghosh

doi:10.3389/fmicb.2019.01303

Abstract

Chromatin architecture influences gene expression and makes specialized chromatin domains. Factors including histone variants, histone modifiers and chromatin remodelers that define chromatin architecture impact chromosome related processes in Candida albicans. In this context, we sought to investigate the roles of the ATP-dependent chromatin remodeler, Remodel the Structure of Chromatin (RSC) in chromosome segregation of C. albicans. Sth1 is the key ATPase component of RSC and has profound roles in different cellular processes in Saccharomyces cerevisiae. We demonstrate that STH1 is an essential gene in C. albicans. The depletion of Sth1 induces pseudohyphal cells, abnormal spindle morphology, sensitivity toward anti-mitotic drugs and global cohesion defect suggesting an important role of Sth1 in kinetochore-microtubule related processes in C. albicans. Strikingly, Sth1 is required to maintain clustered kinetochores revealing the fact that RSC is required in kinetochore integrity. Taken together, we show that RSC plays an important role in various chromatin-templated processes including chromosome segregation in C. albicans.

Highlights

To successfully propagate as a human pathogen, C. albicans relies on the events such as to switch between different morphogenic forms, to express myriad virulence-associated genes and to safeguard its DNA from damage made by the host immune system
We characterized the effect of depletion of Sth1, the ATPase of the Remodel the Structure of Chromatin (RSC) chromatin remodeling complex in C. albicans identified by in silico analysis from CGD
Using three repressible promoters (PCK1, MET3, TET), we convincingly demonstrated that Sth1 is essential for the survival of C. albicans

Summary

Introduction

To successfully propagate as a human pathogen, C. albicans relies on the events such as to switch between different morphogenic forms, to express myriad virulence-associated genes and to safeguard its DNA from damage made by the host immune system. Role of RSC in C. albicans proteins have emerged as potential targets for generation of new antifungal drugs as resistance to the currently available drugs is on rise (Georgopapadakou, 1998; DiDomenico, 1999; Cowen et al, 2002). In this context, a better understanding of the role of epigenetic factors including histone variants, histone modifiers and chromatin remodelers on the biology of C. albicans is needed. Several histone modifying marks and the corresponding writers and erasers of these marks play crucial roles in several biological processes in C. albicans. Loss of the SET3C histone deacetylase complex has been found to cause hyperfilamentation and significantly less mortality during murine systemic candidiasis (Hnisz et al, 2010)

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