Biology

A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in <i>Candida albicans</i>

by Cedric A. Brimacombe, Jordan E. Burke, Jahan-Yar Parsa, Sandra Catania, Teresa R. O’Meara, Jessica N. Witchley, Laura S. Burrack, Hiten D. Madhani, Suzanne M. Noble

Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system required for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire tolerance to antifungal drugs and for nonmeiotic ploidy reduction after mating. We discovered that the ancestor of C. albicans and 2 related pathogens evolved a variant of histone 2A (H2A) that lacks the conserved phosphorylation site for kinetochore-associated Bub1 kinase, a key regulator of chromosome segregation. Using engineered strains, we show that the relative gene dosage of this variant versus canonical H2A controls the fidelity of chromosome segregation and the rate of acquisition of tolerance to antifungal drugs via aneuploidy. Furthermore, whole-genome chromatin precipitation analysis reveals that Centromere Protein A/ Centromeric Histone H3-like Protein (CENP-A/Cse4), a centromeric histone H3 variant that forms the platform of the eukaryotic kinetochore, is depleted from tetraploid-mating products relative to diploid parents and is virtually eliminated from cells exposed to aneuploidy-promoting cues. We conclude that genetically programmed and environmentally induced changes in chromatin can confer the capacity for enhanced evolvability via chromosome missegregation.

Source link

Related posts

Predatory posture and performance in a precocious larval fish targeting evasive copepods [SHORT COMMUNICATION]

Newsemia

Blood Pressure Control Increases Life Expectancy Even in the Most Frail Elderly People

Newsemia

Reduced telomere length in embryos exposed to predator cues [SHORT COMMUNICATION]

Newsemia

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy

COVID-19

COVID-19 (Coronavirus) is a new illness that is having a major effect on all businesses globally LIVE COVID-19 STATISTICS FOR World