Genome-wide replication landscape of Candida glabrata

Area of Science:

• Genomics
• Molecular Biology
• Yeast Biology

Background:

• Candida glabrata, an opportunistic pathogen, is a Saccharomycetaceae yeast.
• It shares a history of whole-genome duplication and gene loss with Saccharomyces cerevisiae.
• Its genome is characterized by numerous large tandem repeats known as megasatellites.

Purpose of the Study:

• To elucidate the replication program of the Candida glabrata genome.
• To understand the general chromosomal organization of C. glabrata.
• To investigate the relationship between replication and megasatellites.

Main Methods:

• Deep-sequencing techniques were employed.
• Chromosome conformation capture (3C) experiments were conducted.
• Autonomously replicating sequences (ARS) capture and growth competition assays were performed.

Main Results:

• 253 replication fork origins were identified genome-wide.
• Early replication was observed for centromeres, HML/HMR loci, and histone genes; late replication for chromosomal breakpoints.
• A 17-bp ARS consensus sequence was identified, more constrained than S. cerevisiae's. Megasatellites were not near origins/termini. Early origins clustered, while non-subtelomeric megasatellites did not.

Conclusions:

• The C. glabrata replication program shows striking similarities to S. cerevisiae, despite evolutionary divergence and megasatellite presence.
• No correlation was found between the replication program and megasatellites.
• Megasatellite formation and propagation may not be directly driven by replication initiation or termination.