Guanine, pairing with cytosine

DMA consists of nucleotides. Nucleotides consist of the bases A, T, G, and C, which are attached to residues of deoxyribose-phosphate. This statement is not entirely correct, since about 1,0% of the cytosine bases in human DNA is modified by a methyl group to form 5-methyl-cytosine. 5-Methy 1-cytosine is formed by an enzyme that flips the cytosine residue out of the DNA helix, methylates it, and flips it back into the helix. 5-Methvl-cytosine pairs with guanine, as does cytosine. 

Base pairing between nucleic acid bases can occur in RNA with adenine pairing with uracil, and cytosine pairing with guanine. However, the pairing is between bases within the same chain, and it does not occur for the whole length of the molecule (e.g. Fig. 6.18). Therefore, RNA is not a double helix, but it does have regions of helical secondary structure. 

A common cause of DNA damage results from spontaneous deamination of bases, for example spontaneous deamination of cytosine forms uracil (Fig. 65.2). Remember uracil is found in RNA and is not normally present in DNA. In RNA, uracil pairs with adenine. Also, remember cytosine pairs with guanine so if the cytosine is deami-nated to uracil an incompatible pairing of the uracil with guanine results that distorts the DNAhehx. This type of single base damage is repaired by the base excision repair process. 

The rules of base pairing (or nucleotide pairing) in DNA are adenine (A) always pairs with thymine (T) cytosine (C) always pairs with guanine (G). 

Mismatch Repair. Mispairs that break the normal base-pairing rules can arise spontaneously due to DNA biosynthetic errors, events associated with genetic recombination and the deamination of methylated cytosine (Modrich, 1987). With the latter, when cytosine deaminates to uracil, an endonuclease enzyme, /V-uracil-DNA glycosylase (Lindahl, 1979), excises the uracil residue before it can pair with adenine at the next replication. However, 5-methyl cytosine deaminates to form thymine and will not be excised by a glycosylase. As a result, thymine exits on one strand paired with guanine on the sister strand, that is, a mismatch. This will result in a spontaneous point mutation if left unrepaired. For this reason, methylated cytosines form spontaneous mutation hot-spots (Miller, 1985). The cell is able to repair mismatches by being able to distinguish between the DNA strand that exists before replication and a newly synthesized strand. 

DNA, adenine (A) pairs with thymine (T) and cytosine (C) pairs with guanine (G). Therefore, when there is an A in one strand of the double-stranded DNA molecule, there is a T in the other strand. When the genetic code is copied from DNA to RNA, the two strands of DNA molecule separate, and the RNA nucleotides pair with nucleotides on each strand of DNA. In this case, the nucleotide that pairs with adenine (A) on the DNA is uracil (U) because RNA does not contain thymine (T). Because of the exact nature of base pairing, the genetic code can be transmitted accurately at each stage of the process. 

Figure 6.2. Molecular architecture of DNA. Each strand of DNA is composed of alternating pentose sugar (deoxyribose) and phosphate moieties linked to each other via phosphodiester linkage. The first carbon position of the sugar is attached to one of the four nitrogenous bases (A, T, G, or C). The two strands are in opposite orientation to each other with respect to a 5 or 3 phosphate group attached to the sugar moiety. Cytosine (C) pairs with guanine (G) via three hydrogen bonds, and adenine (A) pairs with thymine (T). (Reproduced from Textbook of Biochemistry with Clinical Correlations, T. M. Devlin, ed., Wiley, New York, 1982.)...

As adenine undergoes a tautomeric shift, its imino form can base pair with cytosine. The transition shows up in the second generation of DNA replication when cytosine base pairs with guanine. In this manner an A-T base pair is replaced by a C-G base pair. 

DNA wound around one another. The sugar-phosphate backbone is on the outside of the helix, and complementary pairs of bases extend into the center of the helix. The base pairs are held together by hydrogen bonds. Adenine base pairs with thymine, and cytosine base pairs with guanine. The two strands of DNA in the helix are antiparallel to one another. RNA is single stranded. 

In nucleic acids, the pyrimidines match up with specific purine bases. The matching between purines and pyrimidines forms "base-pairs" in which uracil (in RNA) or thymine (in DNA) pairs with adenine. Cytosine pairs with the base guanine in either nucleic acid. 

Figure 22.17 outlines the de novo and salvage synthetic pathways to thymine nucleotides. dUTP, an intermediate in the de novo pathways that begins with UDP, is readily recognized by DNA polymerases and can be incorporated into DNA in place of dXTP. The uracil from a dUMP residue in a DNA strand pairs with adenine (like thymine from a dXMP residue would), so there is no loss of or change in information in the DNA. However, dUMP residues can also arise from spontaneous deamination of dCMP. When this DNA is replicated, a mutation at the site will result because cytosine is meant to pair with guanine, not adenine. 

The base cytosine (XLIX, 4-amino-2(lH)pyrimidone), which, paired with guanine, is present in both DNA and RNA, may be consider the most important parent structure in this class of compounds. Its isomer, isocytosine (L, 2-amino-4(3H)pyrimidone), while not found per se in the nucleic acids, exists as the pyrimidine moiety of guanine (LI), and of the vitamin folic acid (LII). Many analogues of (XLIX) and (L) have been prepared for biological study. Other analogues are found in nature. This section is divided into three parts, including compounds of type (XLIX), (L) and other miscellaneous aminohydroxypyrimidines. Uracils, barbiturates, and 5-hydroxypyrimi-dines which contain amino substituents are found in preceding sections. 

Scheme 29 Adenine-thymine and guanine-cytosine pairs with remote substituents.

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