Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans.
Bloom syndrome is caused by mutation of the Bloom helicase (BLM), a member of the RecQ helicase family. Loss of BLM function results in genomic instability that causes a high incidence of cancer. It has been demonstrated that BLM is important for maintaining genomic stability by playing a role in DNA recombination and repair; however, the exact function of BLM is not clearly understood. 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. We find that the loss of HIM-6 leads to genomic instability as evidenced by an increased number of genomic insertions and deletions, which results in visible random mutant phenotypes. 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. Upon exposure to high temperature, him-6 mutants that are serially passed become sterile demonstrating a mortal germ line phenotype. Our data suggest a model in which loss of HIM-6 results in genomic instability due to an increased number of DNA lesions, which either cannot be repaired and/or are introduced by low fidelity recombination events. The increased level of genomic instability that leads to him-6(ok412) mutants having a shortened life span.
Grabowski
Melissa M
MM
Program in Gene Function and Expression, Program in Molecular Medicine, Aaron Lazare Research Building, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Svrzikapa
Nenad
N
Tissenbaum
Heidi A
HA
D000818:Animals; D017209:Apoptosis; D001816:Bloom Syndrome / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002455:Cell Division; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase; D017353:Gene Deletion; D017930:Genes, Reporter; D018095:Germ-Line Mutation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D008565:Membrane Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D013997:Time Factors; D014965:X-Rays
D029742:Caenorhabditis elegans Proteins; C487047:HIM-6 protein, C elegans; D008565:Membrane Proteins; D009124:Muscle Proteins; C073904:unc-93 protein, C elegans; D049452:Green Fluorescent Proteins