Targeted Inactivation of Nuclear Interaction Partner of ALK Disrupts Meiotic Prophase

Overview

Journal Development

Specialty Biology

Date 2012 Jun 15

PMID 22696294

Citations 15

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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