Types and Consequences of DNA Damage

The consequences of irradiation or alkylation damage include mutagenesis, resulting from erroneous replication of a damaged template base, and cell death, resulting from the inability of the replication apparatus to copy past a damaged site. DNA has a special need for metabolic stability. Its information content must be transmitted virtually intact from one cell to another during cell division or reproduction of an organism. The chemical stability of DNA is maintained in the following two ways:

> 1. By a replication process of very high accuracy that prevents most errors from occurring in the first place.

> 2. By mechanisms for correcting genetic information when DNA suffers damage.

Error reduction systems include proofreading (see here) and the uracil-DNA N-glycosylase system (see here), which protects against mutation arising from deamination of cytosine. Other processes for repairing DNA that is altered either by uncorrected replicative errors or by environmental damage are listed below. Cellular repair systems include the following:

> 1. Direct repair, in which a damaged DNA base is chemically altered to restore the original structure.

> 2. Nucleotide excision repair, in which a section of DNA that contains a damaged site is excised and replaced with normal DNA.

> 3. Base excision repair, which starts with cleavage of the glycosidic bond connecting a damaged base to the DNA sugar-phosphate backbone.

> 4. Recombinational epair, in which newly replicated DNA duplexes undergo genetic recombination, with ultimate removal of the damaged DNA segment.

> 5. Mismatch repair (prokaryotic or eukaryotic), a process that recognizes DNA mismatches created either by replication errors, non-homologous recombination, or damage to one DNA base, and corrects the error.

See also: Pyrimidine Dimers, Thymine Dimers Photoreactivation, , Postreplication Repair, , RecA / SOS Response, Antioxidants (from Chapter 15), Oxygen Metabolism and Human Disease (from Chapter 15).