The analysis of DNA nucleotide polymorphisms is one of the main goals of DNA diagnostics. DNA-dependent enzymes (DNA polymerases and DNA ligases) are widely used to enhance the sensitivity and reliability of systems intended for the detection of point mutations in genetic material. In this article, we have summarized the data on the selectiveness of DNA-dependent enzymes and on the structural factors in enzymes and DNA which influence the effectiveness of mismatch discrimination during enzymatic conversion of oligonucleotide probes on a DNA template. The data presented characterize the sensitivity of a series of DNA-dependent enzymes that are widely used in the detection of noncomplementary base pairs in nucleic acid substrate complexes. We have analyzed the spatial properties of the enzyme-substrate complexes. These properties are vital for the enzymatic reaction and the recognition of perfect DNA-substrates. We also discuss relevant approaches to increasing the selectivity of enzyme-dependent reactions. These approaches involve the use of modified oligonucleotide probes which "disturb" the native structure of the DNA-substrate complexes. KEYWORDS DNA complexes, mismatch, selectivity, DNA ligase, DNA polymerase, modified oligonucleotide probes. ABBREvIATIONS PCR-polymerase chain reaction, NA-nucleic acid, AdD-nucleotidyltransferase domain of DNA ligases, OB-oligonucleotide/oligosaccharide binding domain of DNA ligases, DBD-DNA binding domain of DNA ligases, HhH-motif of DNA ligases helix-hairpin-helix, Zn-zinc-fingers, BRCT-C-terminal domain of DNA ligases, PNA-Peptide Nucleic Acids, LNA-Locked Nucleic Acid, ENA-Ethylene Nucleic Acid, dNTP-deoxyribonucleosidetriphosphate, PPi-inorganic pyrophosphate, mc-main chain of protein backbone.