Late mitotic failure in mice lacking Sak, a polo-like kinase
Late mitotic failure in mice lacking Sak, a polo-like kinase
复制标题
DOI：
10.1016/s0960-9822(01)00117-8
复制
发表时间：
2001-03-20
期刊：
影响因子：
9.2
通讯作者：
Dennis, JW
中科院分区：
文献类型：
--
作者：
Hudson, JW;Kozarova, A;Dennis, JW
Polo-like kinases in yeast, flies, and mammals regulate key events in mitosis, Such events include spindle formation at G2/M, the anaphase promoting complex (APC) at the exit from mitosis, the cleavage structure at cytokinesis, 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 mitotic 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 allele, the first polo-like kinase to be mutated in mice. Sak(-/-) embryos arrested after gastrulation at E7.5, with a marked increase in mitotic and apoptotic cells. Sak(-/-) embryos displayed cells in late anaphase or telophase that continued to express cyclin B1 and phosphorylated histone H3, Our results suggest that Sak is required for the APC-dependent destruction of cyclin B1 and for exit from mitosis in the postgastrulation embryo.
