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mutations
Jun 19, 2002

I watched a really excellent show on nova regarding dna and the complexity of proteins.They mostly explored genetics and the cf defect,but it made me wonder about nukes. Since each one is a faulty copy of the naturally occuring original,how does the drug or body selectively pair the analogue to the viral rna/dna to disrupt the chain elongation and not pair with EVERY dna chain in the body? Obviously,it pairs with mt dna to an extent sometimes creating mutations and causing problems so since all the body's dna consists of a,t,c,g,in some sequence,aren't we inserting a faulty letter into all of or cells. Does this also mean that our own dna is permenantly alterd even if the nuke was discontinued? Also doesn't it make sense that (depending on which nuke is used and it's prevelence in a dna pattern in specific body location)that the emergence of side effects acute versus long term are predicated on the life span of the particular cell of the effected organ? I know this is deep, but I just want to understand why things are happening to my body. Thank you...

Response from Dr. Young

Thanks for the questions-- you've summed up first principles about nucleoside analogues well; yes, the Watson-Crick base pairing between parent and daugther strands of DNA or RNA occurs via the A, C, T (or U) and G bases.

The specificity of particular nucleoside (or nucleotide) analogues -- the ability to relatively inhibit viral enzymes more than your enzymes-- is largely empirical and determined often by chemical moieties (parts) that are not part of the "base" component of the nucleoside.

For most therapeutically active HIV meds, there is a very high degree of specificity. Some medications have a greater effect on one particular DNA polymerase, namely the polymerase gamma of our mitochondria--hence the concerns about mitochondrial toxicity. As you also elude to, the amount of normal nucleosides within the cell also play a role in the likelihood of the drug to compete for binding to the enzyme-- hence, some cell types may be more or less inhibited by the drug.

Hope that you find this helpful. BY



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