cku-80;rrf-3

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Genetic mutants with cku-80, rrf-3 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
25
Lifespan (days)
14.7
Lifespan change (compared to wild type)
4.26%
Phenotype
Using rrf-a 3(pk1426) worms that show increased sensitivity to RNAi when compared with wild type, we observed a slight but significant increase (mean increase aprox 14%) in life span after cku-70(RNAi)
Lifespan comparisons
Double mutant cku-80(RNAi);rrf-3(pk1426) has a lifespan of 14.7 days, while single mutant rrf-3(pk1426) has a lifespan of 14.2 days and wild type has a lifespan of 14.1 days.
Type of interaction
See methods
Partially known monotony. Positive epistasis
Citation
View abstract
McColl G et al., 2005, The C. elegans ortholog of mammalian Ku70, interacts with insulin-like signaling to modulate stress resistance and life span. FASEB J. 19(12):1716-8 16099946 Click here to select all mutants from this PubMed ID in the graph
Abstract
The mammalian Ku heterodimer has important roles in DNA double strand break repair, telomere maintenance, cell cycle checkpoint-arrest, tumor suppression, and cellular stress resistance. To investigate the evolutionarily conserved functions of Ku, we knocked down expression by RNA interference (RNAi) of Ku genes in C. elegans. We found that C. elegans Ku70 (CKU-70) is required for resistance to genotoxic stress, regulates cytotoxic stress responses, and influences aging. The latter effects are dependent on an IGF-1/insulin-like signaling pathway previously shown to affect life span. Reduction of CKU-70 activity amplifies the aging phenotype of long-lived insulin receptor daf-2 mutations in a daf-16-dependent manner. These observations support the view that organismal stress resistance determines life span and Ku70 modulates these effects.

Search genes: cku-80 rrf-3

Entrez ID
Symbol
GenAge
Wormbase ID

175578
cku-80
View on GenAge (cku-80)
WBGene00000520

ATP-dependent DNA helicase II subunit 2;Caenorhabditis KU

Locus: CELE_R07E5.8

Wormbase description: cku-80 encodes an ortholog of human XRCC5 (Ku80; OMIM:194364, antigen of systemic lupus erythematosus); CKU-80 is required for resistance to ionizing radiation (IR) in somatic tissues (such as motor neurons, vulva, uterus, or somatic gonad) and in endoreduplicating intestinal cells, but not in the germline (e.g., in dog-1-induced lesions); CKU-80 is required for growth on high NaCl, probably because excess NaCl induces extensive chromosome breakage; CKU-80 is also required for survival of dauer larvae subjected to IR, and resistance of developing embryos to methyl methane sulfonate; CKU-80 binds CKU-70 in yeast two-hybrid assays, and requires HIM-10 for fully effective DNA repair in somatic cells; by orthology, CKU-80 is expected to function (as a heterodimer with CKU-70) in nonhomologous end-joining of double-stranded breaks in DNA; although CKU-80 is not strongly required in the germline, its absence enhances the hypersensitivity of rad-51(RNAi) germlines to ionizing radiation; mutant cku-80 late-stage embryos or dauer larvae are hypersensitive to radiation-induced DNA damage in somatic cells; after irradiation, cku-80 mutants tend to display various postembryonic phenotypes (such as slow growth, uncoordinated locomotion, impaired egg-laying, or vulval defects) that are enhanced by him-10 mutations, and that are thought to reflect missegregation of fragmented chromosomes; in two-hybrid assays, CKU-80 binds (in addition to CKU-70) DAF-21, CAH-3, and F59A2.5.

Entrez ID
Symbol
GenAge
Wormbase ID

174315
rrf-3
View on GenAge (rrf-3)
WBGene00004510

RNA-dependent RNA polymerase Family

Locus: CELE_F10B5.7

Wormbase description: rrf-3 encodes an RNA-directed RNA polymerase (RdRP) homolog that inhibits somatic RNAi, and thus promotes activity of repeated genes (e.g., multicopy transgenic arrays); the effect of RRF-3 on RNAi is opposite to that of RRF-1 (which stimulates somatic RNAi), which might arise from competition by RRF-3 with RRF-1 or EGO-1 in RNAi formation; rrf-3(allele) or rrf-3(allele2) mutants are hypersensitive to somatic RNAi, and conversely suppress the activity of an integrated rol6 (su1006) transgene.

Orthologs of cku-80;rrf-3 in SynergyAge

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Orthologs of cku-80 in SynergyAge

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Orthologs of rrf-3 in SynergyAge

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SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.