PAT1, an evolutionarily conserved acetyltransferase homologue, is required for multiple steps in the cell cycle

Acetylation has been implicated in many biological processes. Mutations in N-terminal acetyltransferases have been shown to cause a variety of phenotypes in Saccharomyces cerevisiae including activation of heterochromatin, inability to enter G0, and lethality. Histone acetylation has been shown to play a role in transcription regulation, histone deposition and histone displacement during spermatogenesis, although no known histone acetyltransferase is essential. Studies aimed at revealing a role for histone HI in yeast have uncovered a mutation in a putative acetyltransferase, PAT1. The mutant (pat1-1) cells can live only in the presence of vertebrate Hl. PAT1 is essential for mitotic growth in S. cerevisiae; mutant cells depleted of the Pat1p show aberrant cellular and nuclear morphology. PAT1 is required for multiple cell cycle events, including passage through START, DNA synthesis, and proper mitosis through a microtubule-mediated process. The S. pombe PAT1 gene was cloned by complementation and shown to exist as part of a larger protein, the unique portion of which is homologous to a second S. cerevisiae gene. pat1 mutants show a variety of mitotic defects including enhanced chromosome loss, accumulation of multiple nuclei, generation of giant cells, and displays classical cut phenotypes in which cytokinesis occurs in the absence of proper nuclear division and segregation. PAT1 controls multiple processes in cell cycle progression which suggests an essential role for the acetylation of yet unknown substrate(s).