During Drosophila embryogenesis, a cell sheet movement, dorsal closure, allows establishment of the dorsal epidermis. In this morphogenetic process, lateral epithelia undergo a dramatic movement toward the dorsal midline. In the mutant hemipterous (hep), spreading of the epithelia is blocked; in genetically sensitized hep embryos, cell sheet movement can be arrested at any time, indicating hep requirement in maintaining this morphogenetic activity. Further, hep is required for expression in the dorsal epithelium edges of another dorsal closure gene, puckered. The HEP protein is homologous to the Jun kinase kinase (JNKK) group of mitogen-activated protein kinase kinases (MAPKKs). These data suggest that hep functions in a novel Drosophila MAPK pathway, controlling puckered expression and morphogenetic activity of the dorsal epidermis.

Meiotic recombination is induced by the formation of DNA double-strand breaks (DSBs) catalyzed by SPO11, the ortholog of subunit A of TopoVI DNA topoisomerase (TopoVIA). TopoVI activity requires the interaction between A and B subunits. We identified a conserved family of plant and animal proteins [the TOPOVIB-Like (TOPOVIBL) family] that share strong structural similarity to the TopoVIB subunit of TopoVI DNA topoisomerase. We further characterize the meiotic recombination proteins Rec102 (Saccharomyces cerevisiae), Rec6 (Schizosaccharomyces pombe), and MEI-P22 (Drosophila melanogaster) as homologs to the transducer domain of TopoVIB. We demonstrate that the mouse TOPOVIBL protein interacts and forms a complex with SPO11 and is required for meiotic DSB formation. We conclude that meiotic DSBs are catalyzed by a complex involving SPO11 and TOPOVIBL.

Nucleolin (also called C23) is the major nucleolar protein of exponentially growing eukaryotic cells. It is found associated with intranucleolar chromatin and preribosomal particles. Through use of a polyclonal antiserum, nucleolin cDNA clones were isolated from a Chinese hamster ovary cell library constructed in the expression vector Xgtll. The isolated cDNAs encoded a polypeptide containing 679 residues of the 713 amino acids of nucleolin. The amino acid sequence presents several unusual features: in particular, repetitive sequences are found at both ends of the molecule. A repeat, Hy-Thr-Pro-Hy-Lys-Lys-Hy-Hy, in which Hy is a nonpolar residue, is found six times in the NH2-end proximal portion, followed by three acidic stretches containing 25, 25, and 33 glutamic acid or aspartic acid residues. Four potential phosphorylation sites (serines) are also observed in this region. The COOH-terminal proximal portion of the protein carries a glycine-rich region with fairly regularly interspersed phenylalanine and dimethylarginine residues. The two terminal portions of the molecule exhibit unique potential secondary structures: a-helix (NH2 terminus) and extended (COOH terminus). The central region exhibits alternating hydrophobic and hydrophilic stretches. Five potential N glycosylation sites are detected. The structure of this protein may reflect two functions in preribosome biogenesis: interaction with chromatin (NH2 terminus) and with preribosomes (COOH terminus).

No abstract