The Pds1 anaphase inhibitor and Mec1 kinase define distinct checkpoints coupling S phase with mitosis in budding yeast

In most eukaryotic cells, DNA replication is confined to S phase of the cel l cycle [1]. During this interval, S-phase checkpoint controls restrain mit osis until replication is complete [2]. In budding yeast, the anaphase inhi bitor Pds1p has been associated with the checkpoint arrest of mitosis when DNA is damaged or when mitotic spindles have formed aberrantly [3,4], but n ot when DNA replication is blocked with hydroxyurea (HU). Previous studies have implicated the protein kinase Mec1p in S-phase checkpoint control [5], Unlike mec1 mutants, pds1 mutants efficiently inhibit anaphase when replic ation is blocked. This does not, however, exclude an essential S-phase chec kpoint function of Pds1 beyond the early S-phase arrest point of a HU block . Here, we show that Pds1p is an essential component of a previously unsusp ected checkpoint control system that couples the completion of S phase with mitosis, Further, the S-phase checkpoint comprises at least two distinct p athways, A Meet p-dependent pathway operates early in S phase, but a Pds1p- dependent pathway becomes essential part way through S phase.