CDK1 makes the meiotic spindle wait

A delay in cyclin-dependent kinase activity prevents meiotic chromosomes from prematurely attaching to spindle microtubules, Davydenko et al. report.

In somatic cells, the mitotic spindle assembles and forms stable attachments to the kinetochores of sister chromatids in a matter of minutes. In mammalian oocytes undergoing meiosis I, however, multiple microtubule-organizing centers take several hours to assemble a bipolar spindle, and kinetochore–microtubule interactions aren’t stabilized for a few hours after that, probably to prevent chromosomes from forming incorrect attachments while the spindle is still multipolar. How oocytes delay the formation of stable kinetochore–microtubule attachments is unclear, however.

Davydenko et al. wondered whether the cyclin-dependent kinase CDK1 might be involved in timing attachment stabilization. CDK1 activity rises sharply at the beginning of mitosis, but in oocytes the kinase’s activity increases slowly during meiosis I, reaching a peak at the end of metaphase when kinetochore–microtubule attachments are stabilized. Reducing CDK1 activity delayed the formation of stable attachments still further, whereas prematurely boosting CDK1’s function caused oocytes to stabilize their kinetochore–microtubule interactions earlier than normal. This led to frequent errors in chromosome segregation, supporting the idea that oocytes delay attachment stabilization to avoid forming incorrect kinetochore–microtubule connections.

CDK1 phosphorylates numerous substrates, including many kinetochore-associated proteins. Which of these help to stabilize kinetochore–microtubule attachments is an important question for the future, says senior author Michael Lampson.