Alk1 and Alk2 are Two New Cell Cycle-Regulated Haspin-Like Proteins in Budding Yeast

Haspin is a protein kinase identified in mouse and human cells, and genes coding forhaspin-like proteins are present in virtually all eukaryotic genomes sequenced so far. Twohaspin homologues, called Alk1 and Alk2, are present in the yeast Saccharomycescerevisiae. Both Alk1 and Alk2 exhibit a weak auto-kinase activity in vitro, arephosphoproteins in vivo and are hyperphosphorylated in response to DNA damage. Theamount and modification of the two proteins is greatly regulated during the cell cycle. Infact, Alk1 and Alk2 levels peak in mitosis and late-S/G2, respectively, and phosphorylationof both proteins is maximal in mitosis. Control of protein stability plays a major role inAlk2 regulation. The half-life of Alk2 is particularly short in G1; mutagenesis and geneticanalysis indicate that its degradation is controlled by the APC pathway. Overexpression ofALK2, but not of ALK1, causes a mitotic arrest, which is correlated to the kinase activity ofthe protein. This finding, together with its cell cycle regu...