[Antimutagenic role of autonomous 3'-->5'-exonucleases]. 2004

V M Krutiakov

Our own and literary data about antimutagenic role of autonomous 3'-->5'-exonucleases (AE) are analyzed. AE are not bound covalently to DNA polymerases but often involved in replicative complexes. Intracellular overproduction of AE in bacteria is accompanied with the sharp suppression of mutagenesis, whereas the inactivation of AE in bacteria and higher fungi results in the increase of mutation rates by 2-3 orders of magnitude. The addition of AE in biologically meaningful concentrations to DNA polymerases elevates substantially the accuracy of their work in vitro. In these cases, the reverse mutation rates were measured in the DNA from phage (X174 amber 3, whereas the direct mutation rates--in the DNA from phage M13mp2, both being used as primer-templates for DNA synthesis and then transfected into spheroplasts of Escherichia coli. The accuracy of action of nuclease-free DNA polymerases alpha and beta are shown to raise in the presence of AE by 2-3 orders, the accuracy of moderately processive DNA polymerase I--by 2 orders, the accuracy of highly processive DNA polymerase delta--by 5-10 times, though the latter 2 polymerases display and their own 3'-->5'-exonucleolytic activity. AE, involved in the multienzyme DNA polymerase complexes, augment the accuracy of complexes action by 5-10 times. The model of "external" corrective role of AE in DNA biosynthesis is proposed. Study of 30 objects from all 3 kingdoms of live beings (from archae- and eubacteria to mammalia including human) has shown that AE account, as minimum, from 30 to 90% of the total cellular 3'-->5'-exonucleolytic activity. So AE increase essentially the intracellular ratio of values of 3'-->5'-exonuclease to DNA polymerase activities in the very various representatives from a phylogenetic tree that results always in the augmentation of the accuracy of DNA biosynthesis.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D004256 DNA Polymerase I A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. DNA Polymerase alpha,DNA-Dependent DNA Polymerase I,Klenow Fragment,DNA Pol I,DNA Dependent DNA Polymerase I,Polymerase alpha, DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D005092 Exonucleases Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains. Exonuclease,3'-5'-Exonuclease,3'-5'-Exonucleases,5'-3'-Exonuclease,5'-3'-Exonucleases,3' 5' Exonuclease,3' 5' Exonucleases,5' 3' Exonuclease,5' 3' Exonucleases
D005658 Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including MUSHROOMS; YEASTS; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Fungi, Filamentous,Molds,Filamentous Fungi,Filamentous Fungus,Fungus,Fungus, Filamentous,Mold
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D016296 Mutagenesis Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Mutageneses

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