CDC6 requirement for spindle formation during maturation of mouse oocytes

Biol Reprod. 2005 Jan;72(1):188-94. doi: 10.1095/biolreprod.104.035451. Epub 2004 Sep 22.

Abstract

A master regulator of DNA replication, CDC6 also functions in the DNA-replication checkpoint by preventing DNA rereplication. Cyclin-dependent kinases (CDKs) regulate the amount and localization of CDC6 throughout the cell cycle; CDC6 phosphorylation after DNA replication initiation leads to its proteolysis in yeast or translocation to the cytoplasm in mammals. Overexpression of CDC6 during the late S phase prevents entry into the M phase by activating CHEK1 kinase that then inactivates CDK1/cyclin B, which is essential for the G2/M-phase transition. We analyzed the role of CDC6 during resumption of meiosis in mouse oocytes, which are arrested in the first meiotic prophase with low CDK1/cyclin B activity; this is similar to somatic cells at the G2/M-phase border. Overexpression of CDC6 in mouse oocytes does not prevent resumption of meiosis. The RNA interference-mediated knockdown of CDC6, however, reveals a new and unexpected function for CDC6; namely, it is essential for spindle formation in mouse oocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Cyclin B / metabolism
  • Cyclin B1
  • Female
  • Gene Expression Regulation, Enzymologic
  • Meiosis*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oocytes / cytology
  • Oocytes / physiology*
  • RNA Interference
  • RNA, Messenger / metabolism
  • Spindle Apparatus / physiology*

Substances

  • CCNB1 protein, human
  • CDC6 protein, human
  • CDC6 protein, mouse
  • Ccnb1 protein, mouse
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclin B1
  • Nuclear Proteins
  • RNA, Messenger