DNA repair mechanisms

There is strong evidence that DNA adduction by these bulky reactive metabolites of PAHs is far from random, and that there are certain hot spots that are preferentially attacked. Differential steric hindrance and the differential operation of DNA repair mechanisms ensure that particular sites on DNA are subject to stable adduct formation (Purchase 1994). DNA repair mechanisms clearly remove many PAH/ guanine adducts very quickly, but studies with P postlabeling have shown that certain adducts can be very persistent—certainly over many weeks. Evidence for this has been produced in studies on fish and Xenopus (an amphibian Reichert et al. 1991 Waters et al. 1994). 

In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP-ribosylation of proteins and polyADP-ribosylation of nucleoproteins involved in the DNA repair mechanism. 

A survey of investigations on chromosome aberrations in peripheral blood lymphocytes of people exposed to elevated levels of radon in the atmosphere shows non linear dose relationship. At very low doses a sharp increase occured, followed by a plateau. A hypothesis involving DNA repair mechanism is given. 

Additional information about DNA repair is available from the NCBI Science Primer. In the chapter called "What Is A Cell ", scroll down to the heading "DNA Repair Mechanisms." See http /www.ncbi.nlm.nih.gov/Abou1/primei/genetics cell.html. 

Inherited mutations that result in defective DNA repair mechanisms are associated with a predisposition to the development of cancer. Some examples of such genetic diseases are ... 

In addition AS 101 seems to increase DNA repair mechanisms, which conld restore the fnnction of UVB-damaged cells. " ... 

The Michael reaction involves conjugate addition of a nucleophile onto an a,P-unsaturated carbonyl compound, or similar system. Such reactions take place in nature as well, and some can be potentially dangerous to us. For example, the a,P-unsaturated ester ethyl acrylate is a cancer suspect agent. This electrophile can react with biological nucleophiles and, in so doing, bind irreversibly to the nucleophile, rendering it unable to carry out its normal functions. A particularly important enzyme that can act as a nucleophile is DNA polymerase, which is responsible for the synthesis of strands of DNA, especially as part of a DNA repair mechanism (see Section 14.2.2). The nucleophilic centre is a thiol grouping, and this may react with ethyl acrylate as shown. 

Our cells and bodies have evolved to fight off cancer. Specific DNA repair mechanisms work to correct damaged DNA. Our immune system works to isolate and kill rogue cancer cells. Cancer appears to be part of life, an aspect of the aging process, even bad luck. Clearly, however, we have learned that reducing our exposure to certain chemical and physical agents can decrease the likelihood of developing cancer or at least delay its onset. 

Multiple mutations that activate oncogenes or inactivate tumor suppressor genes accumulate due to progressive loss of DNA repair mechanisms and cell cycle control. 

Compounds of this type are extremely important as they can be used for the preparation of catalytic antibodies, synthetic receptors, and model compounds for the investigation of the DNA lesion and recognition steps and DNA repair mechanisms (see Section 10.23.12). 

DNA Repair Mechanisms Vertebrate and plant cells often methylate cytosine in DNA to form 5-methylcytosine (see Fig. 8-5a). In these same cells, a specialized repair system recognizes G-T mismatches and repairs them to G=C base pairs. How might this repair system be advantageous to the cell (Explain in terms of the presence of 5-methylcytosine in the DNA.)... 

In addition to structure-activity relationships, dozens of useful tests have been developed for mutagenicity to germ cells and somatic cells and inferred carcinogenicity. The most straightforward means of testing for effects on DNA is an examination of DNA itself. This is normally difficult to do, so indirect tests are used. One useful test measures the activity of DNA repair mechanisms (unscheduled DNA synthesis) a higher activity is indicative of prior damage to DNA. 

Mutation is a common and naturally occurring event, and most mutations do not lead to deleterious end results since nature has also produced very effective DNA repair mechanisms. Mutagenicity is the chemical alteration of DNA that... 

Metal binding to DNA results in reduced/impaired DNA repair mechanisms, leading to mutagenesis... 

However, even relatively low concentrations of riboflavin can cause damage to DNA under conditions of photolysis, with damage to deoxy-guanosine in isolated DNA, and activation of DNA repair mechanisms in cells in culmre. it is therefore not common practice to use riboflavin supplements as an adjunct... 

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