No abstract

Meiotic chromosomes are organized about a proteinaceous core that forms between replicated sister chromatids. We have isolated a Caenorhabditis elegans gene, him-3, which encodes a meiosis-specific component of chromosome cores with some similarity to the yeast lateral element protein Hop1p. Antibodies raised against HIM-3 localize the protein to condensing chromosomes in early prophase I and to the cores of both synapsed and desynapsed chromosomes. In RNA interference experiments, chromosomes appear to condense normally in the absence of detectable protein but fail to synapse and form chiasmata, indicating that HIM-3 is essential for these processes. Hypomorphs of him-3, although being synapsis proficient, show severe reductions in the frequency of crossing-over, demonstrating that HIM-3 has a role in establishing normal levels of interhomolog exchange. Him-3 mutants also show defects in meiotic chromosome segregation and the persistence of the protein at the chromosome core until the metaphase I-anaphase I transition suggests that HIM-3 may play a role in sister chromatid cohesion. The analysis of him-3 provides the first functional description of a chromosome core component in a multicellular organism and suggests that a mechanistic link exists between the early meiotic events of synapsis and recombination, and later events such as segregation. [Key Words: C. elegans; chromosome core; synapsis; crossing-over; segregation]Received April 12, 1999; revised version accepted July 19, 1999. Meiosis is two specialized cell divisions that result in daughter cells with half the chromosome number of the parental cell. This is accomplished by a single round of DNA replication followed by two divisions, anaphase I and II. Anaphase I is unique in that it segregates homologous chromosomes, each composed of a pair of sister chromatids joined by a single kinetochore, from each other. Most organisms use crossing-over, cytologically evident as chiasmata, to direct the segregation of chromosomes at this division. A decrease in the frequency of crossing-over generally leads to an increase in the nondisjunction of chromosome pairs (for review, see Hawley 1988). For exchange to occur in most organisms, homologous chromosomes must find one another in the prophase nucleus and align themselves throughout their lengths, a process that usually culminates in the formation of a tripartite proteinaceous structure, the synaptonemal complex (SC) (Moses 1968;von Wettstein et al. 1984;Heyting 1996). A prerequisite to the assembly of the mature SC is the polymerization of single proteinaceous axes between sister chromatids, which have been referred to as axial elements or chromosome cores (Moses 1968). The axial elements of homologous chromosomes become aligned and equidistantly separated by the proteins that constitute the central region of the SC and are then referred to as lateral elements. The conserved, highly ordered nature of the SC has raised questions concerning its function and protein composition. Although the localization of axi...

The developmental arrest and intestinal phenotypes of CeTOR deficiency are due to an inhibition of global mRNA translation. Thus, TOR is a major upstream regulator of overall mRNA translation in C. elegans, as in yeast.

Small RNA molecules participate in a variety of activities in the cell: in a process known as RNA interference (RNAi), double-stranded RNA triggers the degradation of messenger RNA that has a matching sequence; the small RNA intermediates of this process can also modify gene expression in the nucleus. Here we show that a single episode of RNAi in the nematode Caenorhabditis elegans can induce transcriptional silencing effects that are inherited indefinitely in the absence of the original trigger. Our findings may prove useful in the ongoing development of RNAi to treat disease.

Programmed cell death (PCD) is an essential and highly orchestrated process that plays a major role in morphogenesis and tissue homeostasis during development. In humans, defects in regulation or execution of cell death lead to diabetes, neurodegenerative disorders, and cancer. Two major types of PCD have been distinguished: the caspase-mediated process of apoptosis and the caspase-independent process involving autophagy. Although apoptosis and autophagy are often activated together in response to stress, the molecular mechanisms underlying their interplay remain unclear. Here we show that BEC-1, the C. elegans ortholog of the yeast and mammalian autophagy proteins Atg6/Vps30 and Beclin 1, is essential for development. We demonstrate that BEC-1 is necessary for the function of the class III PI3 kinase LET-512/Vps34, an essential protein required for autophagy, membrane trafficking, and endocytosis. Furthermore, BEC-1 forms a complex with the antiapoptotic protein CED-9/Bcl-2, and its depletion triggers CED-3/Caspase-dependent PCD. Based on our results, we propose that bec-1 represents a link between autophagy and apoptosis, thus supporting the view that the two processes act in concerted manner in the cell death machinery.