Abnormal base

Cyclophosphamide is an antineoplastic agent that causes DNA cross-linking and abnormal base-pairing through a mechanism called alkylation, hence the name alkylating agent. Cyclophosphamide may also be used in resistant rheumatoid arthritis. 

S-Adenosyl ethionine carries out ethylation reactions or ethyl transfer, and this is presumably involved in the carcinogenesis. Administration of ethionine to animals leads to the production of ethylated bases such as ethyl guanine. This may account for the observed inhibition of RNA polymerase and consequently of RNA synthesis. Incorporation of abnormal bases into nucleic acids and the production of impaired RNA may also lead to the inhibition of protein synthesis and misreading of the genetic code. 

Abnormal bases (uracil, hypoxanthine, xanthine) alkylated bases in some other organisms, pyrimidine dimers... 

Removal of abnormal bases Abnormal bases, such as uracil, which can occur in DNA either by deamination of cytosine or improper incorporation of dUTP instead of dTTP during DNA synthesis, are recognized by specific glycosylases that hydrolytically cleave them from the deoxyribose-phosphate backbone of the strand. This leaves an apyrimidinic site (or apurinic, if a purine was removed), referred to as an AP-site. 

The second type of base-pair transformation, incorporation of an abnormal base analogue, only occurs at... 

Base-excision repair involves the removal of nucleotides that have lost the base moiety as a result of depurination or by the action of DNA glycosylases (enzymes that remove abnormal bases such as deaminated cytosines). As in the other two repair systems, the first step is to remove the deoxyribose 5-phosphate through the action of an endonuclease and a phosphodiesterase which cleave the phosphate backbone and create a single nucleotide gap. 

When bases are lost by depurination or depyrimidination when bases are modified by alkylation, oxidation, or deamination and when abnormal bases (e.g., dUTP, 8-oxo-dGTP) are incorporated into DNA, the resulting lesions are repaired by base excision repair (BER), which, like NER, can occur via distinct subpathways (see Chapter 1 also see Beard and... 

Section 17.81). This is the form normally present in DNA, and, as we have seen, it pairs specifically with cytosine. If guanine tautomerizes (see Section 18.2) to the lactim form, it pairs with thymine instead. Write structural formulas showing the hydrogen bonds in this abnormal base pair. 

Obtain biochemical markers of perfusion abnormalities (base deficit and lactic acid)... 

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