cku-70;daf-2;glp-4

Caenorhabditis KU

Locus: CELE_Y47D3A.4

Wormbase description: cku-70 encodes an ortholog of human XRCC6 (Ku70; OMIM:152690, antigen of systemic lupus erythematosus); CKU-70 is required for resistance to ionizing radiation (IR) in somatic tissues (such as motor neurons, vulva or uterus) and in endoreduplicating intestinal cells, but not in the germline; CKU-70 is also required for survival of dauer larvae subjected to IR, and for resistance of developing embryos to methyl methane sulfonate; CKU-70, unlike CKU-80, inhibits DAF-16-dependent thermotolerance, and slightly shortens normal lifespan; CKU-70 binds CKU-80 in yeast two-hybrid assays, and requires HIM-10 for fully effective DNA repair in somatic cells; by orthology, CKU-70 is expected to function (as a heterodimer with CKU-80) in nonhomologous end-joining of double-stranded breaks in DNA; mutant cku-70 late-stage embryos or dauer larvae are hypersensitive to radiation-induced DNA damage in somatic cells; after irradiation, cku-70 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; cku-70(RNAi) animals show a minor extension of lifespan in an rrf-3(pk1426) mutant background, independently of the presence or absence of either functional DAF-2 or germline cells, but a reduction of lifespan with a loss of DAF-16 activity.

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Valine--tRNA ligase

Locus: CELE_Y87G2A.5

Wormbase description: vrs-2 encodes a predicted cytoplasmic valyl-tRNA synthetase (ValRS), a class I aminoacyl-tRNA synthetase that catalyzes the attachment of valine to its cognate tRNA and is thus required for protein biosynthesis; in C. elegans, VRS-2 activity is required for embryonic and germline development.