PMID:8428592

Citation	Peitsch, MC, Polzar, B, Stephan, H, Crompton, T, MacDonald, HR, Mannherz, HG and Tschopp, J (1993) Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). EMBO J. 12:371-7
Abstract	Cell death by apoptosis occurs in a wide range of physiological events including repertoire selection of lymphocytes and during immune responses in vivo. A hallmark of apoptosis is the internucleosomal DNA degradation for which a Ca2+,Mg(2+)-dependent endonuclease has been postulated. This nuclease activity was extracted from both rat thymocyte and lymph node cell nuclei. When incubated with nuclei harbouring only limited amounts of endogenous nuclease activity, the ladder pattern of DNA fragments characteristic of apoptosis was induced. This extractable nucleolytic activity was immunoprecipitated with antibodies specific for rat deoxyribonuclease I (DNase I) and was inhibited by actin in complex with gelsolin segment 1, strongly pointing to the presence of a DNase I-type enzyme in the nuclear extracts. COS cells transiently transfected with the cDNA of rat parotid DNase I expressed the enzyme, and their nuclei were able to degrade their DNA into oligosome-sized fragments. PCR analysis of mRNA isolated from thymus, lymph node cells and kidney yielded a product identical in size to that from rat parotid DNase I. Immunohistochemical staining with antibodies to rat DNase I confirmed the presence of DNase I antigen in thymocytes and lymph node cells. The tissue distribution of DNase I is thus extended to tissues with no digestive function and to cells which are known to be susceptible to apoptosis. We propose that during apoptosis, an endonuclease indistinguishable from DNase I gains access to the nucleus due to the breakdown of the ER and the nuclear membrane.
Links	PubMed PMC413215
Keywords	Animals; Apoptosis/physiology; Base Sequence; Calcium/pharmacology; Cell Line; DNA/metabolism; Deoxyribonuclease I/isolation & purification; Deoxyribonuclease I/metabolism; Kidney/enzymology; Lymph Nodes/enzymology; Magnesium/pharmacology; Molecular Sequence Data; Nucleosomes/metabolism; Oligodeoxyribonucleotides; Organ Specificity; Parotid Gland/enzymology; Plasmids; Rats; Rats, Inbred Lew; T-Lymphocytes/cytology; T-Lymphocytes/enzymology; Thymus Gland/enzymology; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:DNAS1	enables	GO:0004536: deoxyribonuclease activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
RAT:DNAS1		GO:0004536: deoxyribonuclease activity	ECO:0000314:		F		Fig 4.	complete CACAO 9411

References

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