The
him-6 gene is required for meiotic recombination and genome stability during proliferation of premeiotic cells in Caenorhabditis elegans .
him-6 encodes a putative recQ type of DNA helicase which is homologous to the human BLM (Bloom's Syndrome) gene product. It is also related to the E. coli RecQ helicase, the S. pombe
rqh1+ gene and the S. cervisiae Sgs1 gene. Bloom’s syndrome (BS) is a rare autosomal recessive disorder characterized by genomic instability. The BLM protein is thought to function as antirecombinase in induced recombination resulting, e.g., from blocked replication. The
him-6 gene is predominantly expressed in the germ line. Mutations in
him-6 result in a decrease in meiotic recombination. Oocyte chromosomes of both
him-6(
e1423) and
him-6(
e1104) homozygotes lack chiasmata, suggesting that the chromosomes fail to undergo crossing-over or pairing. However, at pachytene stage, where they are fully paired in wild type animals, no visible defects were observed in
him-6 mutants. Unlike BLM - , however,
him-6 mutations cause no apparent somatic phenotypes. Double mutants for
him-6 and
top-3 (the gene encoding topoiosomerase III a ) exhibits severe defects in the proliferation of the germ line nuclei, a phenotype which is not observed in
top-3 single mutants. The number of nuclei in the gonad is greatly reduced and there are some evidences of chromosomal damage. These nuclei do not appear to progress through meiosis and the chromosomal defects are not suppressed by a mutation in the
spo-11 gene, which is essential for the initiation of meiotic recombination. Altogether, this suggests a profound defect in the ability of
him-6 top-3 double mutants to maintain genome integrity during the stage of germ line proliferation. We propose that HIM-6 has at least two distinct functions. First, it promotes normal levels of meiotic recombination, a novel function for eukaryotic BLM proteins, and second, together with topoisomerase III a , it has DNA repair activity during the proliferation of premeiotic cells. We are currently investigating the possibility that HIM-6 participates in a large repair complex, together with other factors such as, e.g., MRE-11.