The
him-6 gene is necessary for proper chromosome segregation during meiosis in Caenorhabditis elegans. Him-6 animals show an increased nondisjunction frequency for all chromosomes ( Hodgkin et al., Genetics 91, 67-94, 1979), that is associated with a general reduction in recombination (McKim and Zetka, unpublished results, Zetka and Rose, Genetics 141, 1339-1349, 1995) and with a high frequency of unpaired chromosomes in oocytes from both
him-6(
e1423) and
him-6(
e1104) homozygotes. Taken together, these observations suggest that the unpaired chromosomes failed to undergo crossing over and that
him-6 acts at meiotic events prior to disjunction, such as e.g. crossover formation or pairing.
him-6 maps on chromosome IV between
unc-22 and
unc-30. Its position on the genetic map was refined using deficiencies, placing it between
let-93 and
let-99, to the right of
unc-22. Thanks to the sequencing data from the genome consortium and the help of Richard Bruskiewich, a candidate gene coding for a putative DNA helicase was identified in this interval on the cosmid T04A11. While microinjection transformation with T04A11 has so far failed to rescue the
him-6 phenotype, the antisense RNA injection produced a weak, but significant Him phenotype. The length of the cDNA is 3.1 kb which corresponds to the length of the transcript detected on Northern Blot. The sequence of the open reading frame predicts
him-6 to encode a putative DNA helicases related to the E. coli RecQ helicase, with significant homology to the gene product of the human BLM ( Bloom's Syndrome) and the S. pombe
rqh1+ gene. RecQ types of helicases are thought to play a role in regulating genetic exchange and maintaining genomic stability. Sequencing of the mutant alleles revealed that
e1423 contains a T to A transition which gives rise to a stop codon in the helicase domain. The mild allele
e1104 shows a G to Q substitution at a conserved position in the helicase domain. Work is in progress to study the localisation of the
him-6 protein and its role during meiosis.