Targeted inactivation of nuclear interaction partner of ALK disrupts meiotic prophase

Anna Lena Illert, Hiroyuki Kawaguchi, Cristina Antinozzi, Florian Bassermann, Letitia Quintanilla-Martinez, Christine Von Klitzing, Mitsuteru Hiwatari, Christian Peschel, Dirk G. De Rooij, Stephan W. Morris, Marco Barchi, Justus Duyster

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

18 Zitate (Scopus)

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 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 reveal a novel role for NIPA in meiosis.

OriginalspracheEnglisch
Seiten (von - bis)2523-2534
Seitenumfang12
FachzeitschriftDevelopment (Cambridge)
Jahrgang139
Ausgabenummer14
DOIs
PublikationsstatusVeröffentlicht - Juli 2012

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