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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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Submitted August 18, 2004
Returned for revision September 3, 2004
Accepted September 3, 2004

Gamete Biology


CDC6 Requirement for Spindle Formation During Maturation of Mouse Oocytes

Martin Anger , Paula Stein , and Richard M Schultz *

* To whom correspondence should be addressed. E-mail: rschultz{at}mail.sas.upenn.edu.

Abstract
CDC6, a master regulator of DNA replication, also functions in the DNA replication checkpoint by preventing DNA re-replication. 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. Over-expressing CDC6 during late S phase prevents entry into M phase by activating Chk1 kinase that then inactivates CDK1/cyclin B, which is essential for the G2/M 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 border. Over-expressing CDC6 in mouse oocytes does not prevent resumption of meiosis. RNAi-mediated knockdown of CDC6, however, reveals a new and unexpected function for CDC6, namely, it is essential for spindle formation in mouse oocytes.

Key words: Gamete Biology • Kinases • Meiosis • Oocyte development


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