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 a 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 G2/M kinase activity in Nipa–/– spermatocytes. Together, these results show a new unsuspected role for NIPA in meiosis.

Illert, A., L, ., Kawaguchi, H., Antinozzi, C., Bassermann, F., Quintanilla Martinez, L., et al. (2012). Targeted inactivation of nuclear interaction partner of ALK (NIPA) disrupts meiotic prophase. DEVELOPMENT [10.1242/dev.073072].

Targeted inactivation of nuclear interaction partner of ALK (NIPA) disrupts meiotic prophase

BARCHI, MARCO;
2012-01-01

Abstract

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 a 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 G2/M kinase activity in Nipa–/– spermatocytes. Together, these results show a new unsuspected role for NIPA in meiosis.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/16
English
Con Impact Factor ISI
Cell cycle, Knockout mouse, Meiosis, NIPA (ZC3HC1), CCNB1, Checkpoint
Illert, A., L, ., Kawaguchi, H., Antinozzi, C., Bassermann, F., Quintanilla Martinez, L., et al. (2012). Targeted inactivation of nuclear interaction partner of ALK (NIPA) disrupts meiotic prophase. DEVELOPMENT [10.1242/dev.073072].
Illert, A; L, ; Kawaguchi, H; Antinozzi, C; Bassermann, F; Quintanilla Martinez, L; von Klitzing, C; Hiwatari, M; Peschel, C; De Rooij, D; Morris, S; Barchi, M; Duyster, J
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/63428
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