Late mitotic failure in mice lacking Sak, a polo-like kinase

Polo-like kinases in yeast, flies, and mammals regulate key events in mitos is, Such events include spindle formation at G2/M, the anaphase promoting c omplex (APC) at the exit from mitosis, the cleavage structure at cytokinesi s, and DNA damage checkpoints in G2/M, Polo-like kinases are distinguished by two C-terminal polo box (pb) motifs, which localize the enzymes to mitot ic structures. We previously identified Sak, a novel polo-like kinase found in Drosophila and mammals, Here, we demonstrate that the Sak kinase has a functional pb domain that localizes the enzyme to the nucleolus during G2, to the centrosomes in G2/M, and to the cleavage furrow during cytokinesis, To study the role of Sak in embryo development, we generated a Sak null all ele, the first polo-like kinase to be mutated in mice. Sak(-/-) embryos arr ested after gastrulation at E7.5, with a marked increase in mitotic and apo ptotic cells. Sak(-/-) embryos displayed cells in late anaphase or telophas e that continued to express cyclin B1 and phosphorylated histone H3, Our re sults suggest that Sak is required for the APC-dependent destruction of cyc lin B1 and for exit from mitosis in the postgastrulation embryo.