The generation of anteroposterior and dorsoventral polarity is essential during oocyte development. In Drosophila melanogaster, the molecular components involved in establishing these axes have been studied extensively. Formation of each axis is also dependent on the successful repair of DNA double-strand breaks that occur during meiotic recombination. In a recent study (Development 129, 5053–5064 (2002)), Steven Beckendorf and colleagues found that CSN5/Jab1, a component of the COP9 signalosome, interacts with a meiotic checkpoint. Unexpectedly, they found that this interaction influences the formation of both axes.

Translation of gurken, a TGF-α homologue, during two stages of oocyte development is required for the establishment of dorsoventral and anteroposterior axes in Drosophila. Translation of gurken at both stages depends on successful meiotic recombination and the repair of any DNA double-strand breaks generated during this process. The effects of double-strand breaks on Gurken seem to be controlled by a DNA damage checkpoint mediated by Mei-41, a member of the ataxia telangectasia mutated (ATM)/ataxia telangectasia and Rad3-related (ATR) family.

Mutations in CSN5 prevent the normal accumulation of Gurken (see figure) and result in severe defects in polarity. Mutations in CSN5 also affect the modification of Vasa, a protein known to be involved in the translation of Gurken. As the polarity phenotype caused by loss of zygotic CSN5 and the mis-modification of Vasa can be suppressed by mutations in mei-41 (see figure), it seems that in the absence of CSN5, a Mei-41 DNA-damage checkpoint is activated.

Figure 1: Effect of CSN5 mutations on accumulation of Gurken.
figure 1

a, Wild-type germanium showing accumulation of Gurken. b, CSNex21/CSNL4032 germanium with loss of Gurken. c, Loss of mei-41 restores Gurken expression. Image reproduced with permission from the Company of Biologists.

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As the Mei-41 DNA damage checkpoint has previously been linked to the correct localization of Gurken and Vasa, this seems to be the manner by which CSN5 affects polarity. CSN is known to regulate protein stability through deneddylation of cullin, a subunit of the SCF (Skp1/cullin-1/F-box) ubiquitin ligase. Therefore, CSN5 could function to control the stability of proteins involved in the Mei-41 meiotic checkpoint. Although the precise targets of the CSN are unclear, future work will surely identify the precise function of CSN5 in polarity.