Oocyte DNA (red) forms a compact karyosome before meiosis (top). In flies that have a mutant NHK-1, the DNA remains near the nuclear envelope (bottom).

In the large volume of an oocyte, chromosomes huddle together before the meiotic spindle forms. Fashioning this huddled mass—called a karyosome—requires that chromosomes first be released from the nuclear envelope, according to results from Lancaster et al.

Because oocytes lack centrosomes, they assemble spindle microtubules from chromatin. By clustering chromosomes together, karyosomes help make sure that only one spindle is generated. Karyosomes don't form in fly oocytes that lack a kinase called NHK-1. In the new work, the authors found that chromosomes in nhk-1 mutant cells made widespread contacts with the nuclear envelope, whereas in normal cells, the karyosome formed away from the envelope.

The group found that an NHK-1 substrate from fly cells was an envelope-associated protein called BAF. In their model, BAF hooks chromatin to the nuclear envelope during DNA recombination. But phosphorylated BAF unfastened the connection and freed chromosomes to crowd together. Expression of a BAF mutant that could not be phosphorylated maintained a link between the DNA and an inner nuclear envelope protein called Otefin.

The group is now determining whether NHK1, which is itself phosphorylated late in meiosis, might be activated by cell cycle–regulated kinases. The mammalian versions of BAF and NHK-1 are needed for structural changes in the nuclear envelope during mitosis, but no one has yet looked at their role in meiosis.

Reference:

Lancaster, O.M., et al. 2007. J. Cell Biol. 179:817–824.