Centromere DNA mutations induce a mitotic delay in Saccharomyces cerevisiae

Cytological observations of animal cell mitoses have shown that the onset of anaphase is delayed when chromosome attachment to the spindle is spontaneously retarded or experimentally interrupted. This report demonstrates that a centromere DNA (CEN) mutation carried on a single chromosome can induce a cell cycle delay observed as retarded mitosis in the yeast Saccharomyces cerevisiae. A 31-base-pair deletion within centromere DNA element II (CDEII Δ31) that causes chromosome missegregation in only 1% of cell divisions elicited a dramatic mitotic delay phenotype. Other CEN DNA mutations, including mutations in centromere DNA elements I and III, similarly delayed mitosis. Single division pedigree analysis of strains containing the CDEII Δ31 CEN mutation indicated that most (and possibly all) cells experienced delay in each cell cycle and that the delay was not due to increased chromosome copy number. Furthermore, a synchronous population of cells containing the CDEII Δ31 mutation underwent DNA synthesis on schedule with wild-type kinetics, but subsequently exhibited late chromosomal separation and concomitant late cell separation. We speculate that this delay in cell cycle progression before the onset of anaphase provides a mechanism for the stabilization of chromosomes with defective kinetochore structure. Further, we suggest that the delay may be mediated by surveillance at a cell cycle checkpoint that monitors the completion of chromosomal attachment to the spindle.