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Q. Why does thymine replace uracil in DNA?

The difference between DNA and RNA is existence of a hydroxyl (-OH) group on 2' carbon of the ribose sugar in the backbone. Removal of 2' hydroxyl groups from DNA doesn't occur after the DNA has been synthesized, but instead of 2' hydroxyl groups are removed from the nucleotides before they are incorporated into DNA. During nucleotide synthesis, a portion of nucleotide monophosphates (NMP's) are dehydroxylated to 2'-deoxynucleotide monophosphates (dNMP's). This means thatGMP, AMP, CMP, and UMP are converted into dGMP, dAMP, dCMP, and dUMP, correspondingly. Though, before being incorporated into the chromosomes, another modification, using folic acid as a catalyst, methylates the uracil in dUMP to form a thymine making it dTMP. After further phosphorylation, dGTP, dATP, dCTP, and dTTP can be used as building blocks to construct DNA.

The significant thing to notice is that whereas uracil exists as both uridine (U) and deoxyuridine (dU), thymine only exists as deoxy-thymidine (dT). So the question becomes: Why do cells go to the trouble of methylating uracil to thymine before it can be used in DNA? The answer is: methylation protects the DNA. Besideusing dTin place of dU, most organisms also use several enzymes to modify DNA after it has been synthesized. Two such enzymes, dam and dcm methylate adenines and cytosines, correspondingly, along the entire DNA strand. This methylation makes DNA unrecognizable to many Nucleases (enzymes which break down DNA and RNA), so that it can't be easily attacked by invaders, such as viruses or certain bacteria. Obviously, methylating nucleotides before they are incorporated makes sure that entire strand of DNA is protected. Thymine also protects DNA in another way. If you look at components of nucleic acids, phosphates, sugars, and bases you see that they are all very hydrophilic (water soluble). Obviously, adding a hydrophobic (water insoluble) methyl group to part of the DNA is going to change characteristics of the molecule. The major effect is that methyl group will be repelled by the rest of DNA, moving it to a fixed position in the major groove of helix. This solves a vital problem with uracil - though it prefers adenine, uracil can base-pair with almost any other base, including itself, relying on how it situates itself in the helix. By tacking it down to a single conformation, methyl group restricts uracil (thymine) to pairing only with adenine. This greatly improves the efficiency of DNA replication, by reducing rate of mismatches, and thus mutations.

To sum up: Replacement of thymine for uracil inDNA protects the DNA from attack and maintains the fidelity of DNA replication.

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