Biology subjects

Jaitly, P.

Publications and source records attributed to Jaitly, P..

2 recordsLinked to original sources

bioRxiv2021

A phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans

Chromosomal instability in fungal pathogens caused by cell division errors is associated with antifungal drug resistance. To identify mechanisms underlying such instability and to uncover new potential antifungal targets, we conducted an overexpression screen monitoring chromosomal stability in the human fungal pathogen Candida albicans. Analysis of ~1000 genes uncovered six chromosomal stability (CSA) genes, five of which are related to cell division genes in other organisms. The sixth gene, CSA6, is selectively present in the CUG-Ser clade species that includes C. albicans and other human fungal pathogens. The protein encoded by CSA6 localizes to the spindle pole bodies, is required for exit from mitosis, and induces a checkpoint-dependent metaphase arrest upon overexpression. Together, Csa6 defines an essential CUG-Ser fungal clade-specific cell cycle progression factor, highlighting the existence of phylogenetically-restricted cell division genes which may serve as potential unique therapeutic targets. TeaserCsa6 is essential for mitotic progression and mitotic exit in the human fungal pathogen Candida albicans.

cell biology↗

bioRxiv2018

DNA replication initiator proteins facilitate CENPA loading on early replicating compact chromatin

Spatiotemporal regulation in DNA replication maintains kinetochore stability. The epigenetically regulated centromeres (CENs) in the budding yeast Candida albicans have unique DNA sequences, replicate early and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of replication initiation protein Orc4 reveals its abundance at all CENs in C. albicans. Orc4 associates with four different DNA motifs, one of which coincides with tRNA genes. Hi-C combined with genome-wide replication timing analyses identify enriched interactions among early or late replicating Orc4-bound regions. A simulated polymer model of chromosomes reveals that early replicating and strongly enriched Orc4-bound sites localize towards the kinetochores. Orc4 is constitutively localized to CENs, and both Orc4 and Mcm2 stabilize CENPA. CENPA chaperone Scm3 localizes at the kinetochore during anaphase, coinciding with the loading time of CENPA. We propose that this spatiotemporal nuclear localization of Orc4, with Mcm2 and Scm3, recruits CENPA and stabilizes centromeric chromatin.

molecular biology↗