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BOR - Papers in Press, published online ahead of print September 22, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.035451
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BIOLOGY OF REPRODUCTION 72, 188–194 (2005)
DOI: 10.1095/biolreprod.104.035451
© 2005 by the Society for the Study of Reproduction, Inc.

CDC6 Requirement for Spindle Formation During Maturation of Mouse Oocytes1

Martin Anger, Paula Stein, and Richard M. Schultz2

Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018

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.

1 Supported by a grant from the National Institutes of Health (HD22681) to R.M.S. M.A. and P.S. contributed equally to this work.

2 Correspondence: Richard Schultz, Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104-6018. FAX: 215 898 8780; rschultz{at}mail.sas.upenn.edu




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Copyright © 2005 by the Society for the Study of Reproduction.