Disease relevance of nuc-1

• A family history of deoxyribonuclease II: surprises from Trichinella spiralis and Burkholderia pseudomallei [1].

High impact information on nuc-1

• We used the TUNEL technique to assay DNA degradation in nuc-1 and other mutants defective in programmed cell death and discovered that TUNEL labels apoptotic cells only during a transient intermediate stage [2].
• We have previously implicated deoxyribonuclease II (DNase II) as an endonuclease responsible for DNA digestion during apoptosis [3].
• Considering that DNase II is normally active only at low pH, it was surprising that transfection induced chromatin condensation [3].
• To determine whether overexpression of DNase II induces apoptosis in Chinese hamster ovary cells, the cDNA was cotransfected with a plasmid encoding green fluorescent protein [3].
• Previously, three genes were known to be involved in eliminating cell corpses in the nematode Caenorhabditis elegans: ced-1, ced-2 and nuc-1 [4].

Biological context of nuc-1

• Furthermore, nuc-1 transgenic lines carrying the wild-type C07B5.5 locus demonstrated a complete complementation of the nuc-1 mutant phenotype [5].
• The lethality of DNase II-knockout mice is likely the result of multiple developmental defects, the most obvious being a loss of definitive erythropoiesis [6].
• Subsequent investigations also suggested that DNase II was important for DNA fragmentation and degradation during cell death [6].
• Deoxyribonuclease II (DNase II) has been implicated in diverse functions including degradation of foreign DNA, genomic instability, and in mediating the DNA digestion associated with apoptosis [7].

Anatomical context of nuc-1

• F2-P3E3 staining is present within LMP-1::GFP labeled organelles in the intestinal primordium and is coincident with persistent DNA that has been phagocytosed in nuc-1(-) embryos, suggesting that it labels phagosomes [8].
• As expected, expression of a dnase II-RNAi construct in flies resulted in a dramatic reduction of DNase II activity and a significant decrease in total hemocyte numbers [9].

Other interactions of nuc-1

• Subsequent analysis of crude C. elegans protein extracts revealed that wild-type animals contained a potent endonuclease activity with a cleavage preference similar to DNase II, while nuc-1 mutant worms demonstrated a marked reduction in this nuclease activity [5].

Analytical, diagnostic and therapeutic context of nuc-1

• Sequence analysis of C07B5.5 DNA and mRNA also revealed that nuc-1(e1392), but not wild-type animals contained a nonsense mutation within the CO7B5.5 coding region [5].
• In this report, we describe the molecular cloning and characterization of DLAD, a novel mammalian deoxy-ribonuclease homologous to DNase II [10].

References