Disease relevance of helicase

• Several eukaryotic homologs of the Escherichia coli RecQ DNA helicase have been found [1].
• Bloom syndrome is caused by mutation of the Bloom helicase (BLM), a member of the RecQ helicase family [2].

High impact information on helicase

• Blm-deficient mice, like Bloom syndrome patients, have increased frequencies of mitotic recombination owing to a mutation in the RecQ protein-like-3 helicase gene [3].
• Mutations in him-6 result in an enhanced irradiation sensitivity, a partially defective S-phase checkpoint, and in reduced levels of DNA-damage induced apoptosis [4].
• In rec-1; him-6 and rec-1; him-14 homozygotes the frequency of crossing over was characteristic of the Him mutant phenotype, whereas the distribution of the reduced number of exchanges was characteristic of the Rec-1 pattern [5].
• The phenotypes in the germ cells of him-6(e1104);top3alpha(RNAi) were also observed in the progeny produced by double RNA interference of the top3alpha and him-6 gene expression, though at a reduced level [6].
• BACKGROUND: Among the four RecQ homologues predicted from the Caenorhabditis elegans genomic DNA sequence, T04A11.6 is most similar to Bloom syndrome's protein in humans [6].

Biological context of helicase

• To determine the mechanism by which BLM controls genomic stability in vivo, we examined the phenotypes caused by mutation of the C. elegans BLM helicase ortholog, HIM-6 [2].
• In addition to the mutator phenotype, him-6 mutants have a low brood size, a high incidence of males, a shortened life span, and an increased amount of germ line apoptosis [2].
• Unlike rec-1, individuals homozygous for him-6 and him-14 had an overall reduction in the amount of crossing over accompanied by a high frequency of nondisjunction and reduced egg hatching [5].
• The mutation him-6 (e1423) leads to generalized chromosomal nondisjunction during meiosis in oogenesis and spermatogenesis of C. elegans [7].
• When strain him-6(e1104) containing a missense him-6 mutation was irradiated with gamma-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos [8].

Other interactions of helicase

• (v) Three meiotic mutants, him-3, him-6, and him-8, had no effect on somatic loss of the duplications but did reduce the frequency of breakage events [9].

References