Details

Autor(en) / Beteiligte

• Hudson, J.W.
• Kozarova, A.
• Cheung, P.
• Macmillan, J.C.
• Swallow, C.J.
• Cross, J.C.
• Dennis, J.W.

Titel

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

Ist Teil von

• Current biology, 2001-03, Vol.11 (6), p.441-446

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2001

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.