Enzyme repair system

DNA repair Because most mutations are very damaging, even the simplest organisms have enzyme systems that repair DNA. These DNA repair systems are important because genetic defects in them can cause some human diseases. 

The excision repair system consists of several enzymes, each involved in several steps. First, the error must be recognized. For example, an... 

However, complex error corrections (by repair enzymes) permit a great reduction in the error rate. Such repair systems were not available to primitive replicators, so they needed to survive with error rates of more than 1 100 this reduced the size of the genome to around 100 bases (nucleotides). This became obvious in work done by Saul Spiegelmann (1967) and the Eigen group (Biebricher et al 1981). 

An in-depth study of DNA repair systems (Aravind et al., 1999a) has concluded that few, if any, repair proteins occur with identical collinear domain arrangements in all three kingdoms of life. Approximately 10 enzyme families of adenosine triphosphatases (ATPases), photolyases, helicases, and nucleases were identified that are all likely to have been present in the cenancestor. These enzymatic domains are accompanied in DNA repair proteins by numerous regulatory domains. This indicates that the domain architectures of these proteins are labile, with incremental addition and/or subtraction of domains to conserved cores to be a common phenomenon except in the most closely related species. 

Due to the many damaging influences on the DNA, it is essential for the cell that DNA damage can be repaired. The repair systems involved, such as the enzyme apparatus of excision repair, the alkyl transferases and the mispairing repair system, operate almost without error and can repair the vast majority of DNA damage. A deficit in the repair... 

The body s natural defenses against overenthusiastic oxidation include a-lipoic acid, reduced glutathione, ascorbic acid, the tocopherols, the carotenoids, and a number of enzymes such as epoxide hydrolase and the like. Very efficient DNA repair systems also operate defensively. These various means are remarkably effective, but DNA assault is continuous, cumulative, and implacable. Thus, many degenerative diseases are associated with aging because of the gradual slippage in functional fidelity of cellular machinery which occurs with age. 

Reoviruses 248. See also front cover Repair systems 16 Replication cycle. See Cell cycle Repression of enzyme synthesis 536, 538, 539 Repressor(s) 76, 239... 

Inhibition of DNA repair may result in an adverse event within the cell. As(III) has been shown to inhibit DNA ligase in vitro, but it does not appear to occur by the direct interaction of As(III) with this repair enzyme (Li and Rossman, 1989). It has been suggested that As(III) alters redox levels or affects signal transduction pathways involved with DNA ligase (Hu, Su and Snow, 1998). The nucleotide excision repair system is also impaired by arsenic (Okui and Fujiwara, 1986 Hartwig et al., 1997). 

When DNA damage occurs, a number of repair systems can increase the cell s probability of survival. Several assays for genotoxicity rely on indirect measurement of the effects of these repair systems. TWo assays (the B. subtilis rec assay and the E. ooli DNA polymerase assay) measure reduction in the survival of chemically treated cells that lack at least one DNA-repair enzyme, compared with cells that have an intact repair system.198 373... 

Cells have evolved ways of preventing mutations caused by either mechanism. First, cells contain an enzyme, dUTPase, which hydrolyses dUTP to dUMP. Thus the triphosphate substrate is taken away from DNA polymerase before it can serve as a substrate. Secondly, U residues in DNA from whatever source cause the gap repair system to... 

The repair system removes damaged biomolecules before cell metabolism or viability has been altered due to their accumulation. Oxidatively damaged nucleic acids are repaired by specific enzymes, oxidized proteins are removed by proteolytic systems, and... 

One possibihty for minimizing oxidized protein damage is the thiol repair (Fig. 3). This repair system requires either glutathione or the thioredoxin system. The thioredoxin/thioredoxin reductase repair system [10] is able to reduce disulfide bonds. It can dethiolate protein disulfides and thus is an extremely important regulator for redox homeostasis in the cells. Thioredoxin is a smaU ubiquitous protein that contains a pair of cysteines that undergo reversible oxidation and are re-reduced by the enzyme thioredoxine reductase. The thioredoxin reductase transfers electrons from NADPH to thioredoxin via a flavin. 

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