Mutations in the unc-51 gene of the nematode Caenorhabditis elegans result in various abnormalities in axonal elongation and axonal structures. We cloned the UDC-51 gene by tagging with the transposon Tel. The wild-type unc-51 gene, which rescued the mutant phenotypes, encodes a novel serine/threonine kinase of 856 amino acids. Mutation sites were identified in the unc-51 gene of six mutants. A Lys -^ Met mutation created in vitro in the kinase domain led to the loss of rescuing activity and was dominant negative, indicating that the kinase domain of Unc-51 is essential for the function. Expression of an unc-51/lacZ fusion gene was observed in many neurons at all stages. We propose that protein phosphorylation by the unc-51 product is important for axonal elongation and possibly for axonal guidance.

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Telomeres are specialized structures located at the ends of linear eukaryotic chromosomes that ensure their complete replication and protect them from fusion and degradation. We report here the characterization of the telomeres of the nematode Caenorhabditis elegans. We show that the chromosomes terminate in 4-9 kb of tandem repeats of the sequence TTAGGC. Furthermore, we have isolated clones corresponding to 11 of the 12 C. elegans telomeres. Their subtelomeric sequences are all different from each other, demonstrating that the terminal TTAGGC repeats are sufficient for general chromosomal capping functions. Finally, we demonstrate that the me8 meiotic mutant, which is defective in X chromosome crossing over and segregation, bears a terminal deficiency that was healed by the addition of telomeric repeats, presumably by the activity of a telomerase enzyme. The 11 cloned telomeres represent an important advance for the completion of the physical map and for the determination of the entire sequence of the C. elegans genome.Telomeres are specialized structures that protect chromosome ends against degradation and fusion and ensure their complete replication. Cytological studies suggest that telomeres may also play a role in the spatial arrangement of the chromosome ends in the nucleus. In most species that have been investigated, telomeric DNA is marked by the presence of long stretches of conserved short tandem repeats that are synthesized by RNAdependent DNA polymerases (telomerases) (1).For a variety of reasons, we think that the nematode Caenorhabditis elegans, a well-characterized experimental organism that is amenable to a combination of genetic, cytological, and biochemical approaches, represents an excellent model system for a molecular and genetic analysis of telomeres. First, C. elegans has the best-developed physical map of any metazoan organism, with over 95% of the genome represented on contiguous stretches of overlapping yeast artificial chromosome (YAC) and cosmid clones (2-4) and over 35% of the genomic DNA sequenced (5-7). Nevertheless, the chromosome ends are notably missing from the map, accounting for most of the few remaining gaps. The reasons for this may be largely systematic, since the methods used to construct the map were biased against isolation and mapping of terminal clones. Cloning the C. elegans telomeres using methods specifically designed to isolate terminal clones will provide a key resource for filling in these terminal gaps, thereby allowing completion of the physical map and the genome sequence. Second, the end regions of the C. elegans chromosomes have been implicated in several important meiotic functions, including nuclear membrane attachment, pairing and synapsis of homologous chromosomes, and kinetic activity during the meiotic divisions (reviewed in refs. 8-10). Thus, completing the physical maps of the chromosome ends may facilitate the molecular dissection of chromosomal domains involved in meiosis.Third, cloning of the C. elegans telomeres, coupled with the study...

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