A temperature-sensitive mutant screen reveals a translational stress-induced cell-cycle arrest in a thermophilic...

The homology of the archaeal and eukaryotic ribosome along with similarities in their apparatus involved in DNA replication and transcription provide key pieces of evidence underpinning the idea that eukaryotes acquired their core information processing machinery from archaea. Building on this discovery, reverse genetics in archaea has been used to study the functions of many archaeal proteins with eukaryotic homologues. Despite this progress, our general understanding of archaeal growth and division remains unclear, partly because of difficulties of carrying out unbiased genetic screens in archaeal relatives of eukaryotes. Here, we have used a screen of temperature-sensitive mutants in Sulfolobus acidocaldarius to identify regulators of cell growth and division. First, flow cytometry was used to define cellular DNA content - identifying a set of mutants defective in cell-cycle progression at elevated growth temperatures. Genome sequencing and plasmid rescuethen identified a point mutation in the large ribosomal subunit that inhibits translation and prevents growth and entry into division at the restrictive temperature. Taken together, these data reveal a link between translation and cell-cycle control in Sulfolobus, and show how forward genetic screens in archaea can be used to further explore similarities and differences in the cell biology of archaea, bacteria, and eukaryotes.