CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint

Sergey Doronkin1, Inna Djagaeva, Steven K Beckendorf

  • 1Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley 94720, USA.

Development (Cambridge, England)
|October 25, 2002
PubMed

Insights

The COP9 signalosome subunit CSN5 is crucial for Drosophila oocyte development, regulating meiotic progression and axis formation by controlling Gurken protein translation via a DNA repair checkpoint.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Genetics

Background:

  • The COP9 signalosome (CSN) complex regulates diverse cellular processes, including protein degradation and signaling pathways, across various organisms.
  • While CSN's roles are established in yeast, plants, and mammals, its specific functions in Drosophila development are less understood.

Purpose of the Study:

  • To investigate the role of CSN5/JAB1, a CSN subunit, in Drosophila oogenesis and early development.
  • To elucidate the molecular mechanisms by which CSN5 influences meiotic progression and axis patterning in the oocyte.

Main Methods:

  • Analysis of CSN5/JAB1 mutant phenotypes during Drosophila oogenesis.
  • Investigating the impact of CSN5 mutations on the accumulation and translation of the EGFR ligand Gurken.
  • Examining the modification status of Vasa protein in CSN5 mutants.
  • Genetic interaction studies with genes involved in DNA repair checkpoints (mei-41) and double-strand break formation (mei-W68).

Main Results:

  • CSN5 is essential for meiotic progression and the establishment of anterior-posterior (AP) and dorsal-ventral (DV) axes in the Drosophila oocyte.
  • CSN5 mutations lead to reduced Gurken protein accumulation and aberrant modification of Vasa, a key regulator of Gurken translation.
  • The CSN5 phenotype is suppressed by mutations in mei-41 (DNA damage checkpoint) and mei-W68 (double-strand break formation), indicating a link to DNA repair pathways.

Conclusions:

  • CSN5 regulates Drosophila oocyte axis formation through checkpoint-dependent translational control of Gurken, similar to spindle-class genes.
  • This study reveals a novel connection between DNA repair mechanisms, axis formation, and the COP9 signalosome in Drosophila development.

Related Concept Videos

Meiosis II01:57

Meiosis II

Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each containing...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Meiosis I03:09

Meiosis I

Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
Nondisjunction01:21

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...