Caenorhabditis elegans

CPS-6

CELE_C41D11.8, C41D11.8
cps-6 encodes an ortholog of human mitochondrial endonuclease G (EndoG) that promotes apoptosis, and is required to degrade nicked (TUNEL-positive) DNA in apoptotic cells; transgenic CPS-6 is localized to mitochondria, but transgenic CPS-6 lacking a mitochondrial localization sequence is found in nuclei, and nuclei may be the in vivo target of CPS-6 after its activation by CED-3; CPS-6 has magnesium-dependent nuclease activity in vitro and can degrade both single- and double-stranded DNA, as well as single-stranded RNA; CPS-6 also preferentially binds G-tract DNA in vitro; cps-6(sm116) and cps-6(RNAi) animals have delayed CED-3-induced apoptosis, and cps-6(sm116) suppresses a constitutively active ced-3 transgene; cps-6(sm116) can be transgenically rescued by mouse EndoG; CPS-6 binds WAH-1 (an apoptosis-inducing factor ortholog) in vitro, WAH-1 binding enhances CPS-6's endonuclease activity, and constitutive transgenic coexpression of cps-6 with wah-1 induces cell death not seen with constitutive expression of either cps-6 or wah-1 alone; CPS-6 binds CRN-1 (a flap endonuclease ortholog) in vitro, and may form a large complex in vivo with CRN-1, CRN-4, CRN-5, CYP-13, and WAH-1; CRN-1 enhances CPS-6's endonuclease activity in vitro, CPS-6 enhances CRN-1's gap-dependent endonuclease and 5'-3' exonuclease activities, and cps-6 is required for excess cell deaths induced by a crn-1 transgene.
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