cku-70;daf-16

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.

---

Forkhead box protein O;hypothetical protein

---

Locus: CELE_R13H8.1

---

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

---