Inhibition of deoxyribonuclease I by actin is to protect cells from premature cell death.
Deoxyribonuclease I (Dnase1) is the major extracellular endonuclease. It is secreted by digestive glands into the alimentary tract and into the plasma, lacrimal fluid and urine by hepatocytes, lacrimal glands and renal proximal tubular cells, respectively. In many species the activity of Dnase1 is inhibited by monomeric actin. However, the biological significance of this high affinity interaction is unknown. We generated a Dnase1 mutant with extremely reduced actin binding capacity. EGFP-constructs of wild-type and mutant Dnase1 were transfected into MCF-7 breast cancer cells and apoptosis or necrosis was induced by staurosporine or oxidative stress. During apoptosis faster chromatin fragmentation occurred in cells transfected with mutant Dnase1. When wt (wild-type)- or mutated Dnase1 were added to cells after induction of necrosis, faster chromatin degradation occurred in the presence of mutant Dnase1. Inclusion of actin under these conditions inhibited chromatin degradation by wt- but not by mutated Dnase1. Thus, inhibition of Dnase1 by actin may serve as a self-protection mechanism against premature DNA degradation during cell damage.
Eulitz
Dirk
D
Department of Anatomy and Embryology, Ruhr-University Bochum, Germany. Dirk.Eulitz@rub.de
Mannherz
Hans Georg
HG
D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D019610:Cytoprotection; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D009336:Necrosis / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering; D014407:Tumor Cells, Cultured
D000199:Actins; D002843:Chromatin; D050505:Mutant Proteins; D003850:Deoxyribonuclease I