期刊
DEVELOPMENT
卷 139, 期 14, 页码 2523-2534出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.073072
关键词
Cell cycle; Knockout mouse; Meiosis; NIPA (ZC3HC1); CCNB1; Checkpoint
资金
- Deutsche Forschungsgemeinschaft (DFG) [DU227/3-1]
- Wilhelm Sander Stiftung [2007.043.1]
- Technical University of Munich [KKF-B07-08]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [MFAG] [4765]
- National cancer Institute (NCI) [CA69129, CA21765]
- American Lebanese Syrian Associated Charities (ALSAC, St Jude Children's Research Hospital)
- German Research Foundation [BA 2851/3-1]
- German Cancer Aid [109543]
- Grants-in-Aid for Scientific Research [23591552] Funding Source: KAKEN
NIPA (nuclear interaction partner of ALK) is an F-box-like protein that monitors the timing of mitotic entry. Constitutively active NIPA delays mitotic entry by preventing accumulation of nuclear cyclin B1. Here, we have investigated the consequences of Nipa inactivation by using a conditional knockout strategy. Nipa-deficient animals are viable but show a lower birth rate and reduced body weight. Furthermore, Nipa-deficient males are sterile owing to a block of spermatogenesis during meiotic prophase. Whereas Nipa(-/-) mouse embryonic fibroblasts show no severe phenotype, Nipa(-/-) spermatocytes arrest during stage IV of the epithelial cycle with subsequent TUNEL-positive apoptosis resulting from improper synapsis, defects in the repair of DNA double-stranded breaks and synaptonemal complex formation. Moreover, we show nuclear accumulation of cyclin B1 with a subsequent premature increase in G(2)/M kinase activity in Nipa(-/-) spermatocytes. Together, these results reveal a novel role for NIPA in meiosis.
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