DNA Degradation and Its Defects

DNA is one of the most essential molecules in organisms, containing all the information necessary for organisms to live. It replicates and provides a mechanism for heredity and evolution. Various events cause the degradation of DNA into nucleotides. DNA also has a darker side that has only recently been recognized; DNA that is not properly degraded causes various diseases. In this review, we discuss four deoxyribonucleases that function in the nucleus, cytosol, and lysosomes, and how undigested DNA causes such diseases as cancer, cataract, and autoinflammation. Studies on the biochemical and physiological functions of deoxyribonucleases should continue to increase our understanding of cellular functions and human diseases.Chromosomal DNA replicates semiconservatively; it is constructed in growing cells and is not thereafter metabolized within the cell. Both animal and plant cells carry several DNA-degrading enzymes (called deoxyribonuclease, or DNase). DNases have primarily been regarded as enzymes that digest the DNA in food into nucleotides for use in rebuilding the organism''s own DNA, just as proteases digest food proteins (from fish, meat, or vegetables) into amino acids. For many years, studies on DNases focused almost exclusively on their enzymatic activity, and not on their physiological or pathological roles. This changed with the discovery that chromosomal DNA is digested in apoptotic cells (Wyllie 1980). Since then, DNA degradation has been observed in the differentiation processes of red blood cells, skin, and optic lens (Bassnett 2002; McGrath et al. 2008; Eckhart et al. 2013). Reverse-transcribed DNA from endogenous retro elements is digested in the cytoplasm (Stetson et al. 2008), and in inflammation, extracellular DNA released from dead cells is actively degraded in the circulation (Rekvig and Mortensen 2012). Here, we discuss how DNA is digested in physiological and pathological settings, and what happens to the organism if DNA is not properly digested.