The Spd1p S phase inhibitor can activate the DNA replication checkpoint pathway in fission yeast

Spd1p (for S phase delayed) is a cell cycle inhibitor in Schizosaccharomyce s pombe. Spd1p overexpression blocks the onset of both S phase and mitosis. In this study, we have investigated the mechanisms by which Spd1p overexpr ession blocks cell cycle progression, focussing on the block over mitotic o nset. High levels of Spd1p lead to an increase in Y15 phosphorylation of Cd c2p and we show that the block over G(2) requires the Wee1p kinase and is d ependent on the rad and chk1/cds1 checkpoint genes. We propose that high le vels of Spd1p in G(2) cells activate the DNA replication checkpoint control , which leads to a Wee1p-dependent increase of Cdc2p Y15 phosphorylation bl ocking onset of mitosis. The Spd1p block at S phase onset may act by interf ering directly with DNA replication, and also activates the G(2) rad/hus ch eckpoint pathway to block mitosis.