Ok, heres a DNA question. Or maybe a chemistry question. Either way, i cant seem to find the answer anywhere. Its kinda short…here goes…
Nucleotides join to form polynucleotides when the pyrophosphates of one gets cleaved off and the phosphate end of the nucleotide joins with the hydroxyl end of another right?
So why izzit that new nucleotides can only join at the 3’ end of a polynucleotide? why not the new nucleotide fit itself onto the conventional head instead of the conventional tail?
Another question I really wish I had the time to answer. I think the reason has to do with the way DNA synthesis ended up evolving – the binding site of DNA polymerase is shaped in such a way that the existing polynucleotide fits into the polymerase with the 3’ end at the active site, rather than the 5’ end, and the 5’ end of the incoming nucleotide to be added fits at the active site. The 5’ end will not fit at the active site, though I believe there are (extremely rare) polymerases that add at the 5’ end. I don’t recall a specific chemical reason why addition at the 3’ end is favorable, though I might recall or find one if I had more time to think about it/look it up. You might find something more here
A related issue which you might find interesting is the reason why deoxyribonucleic acid is used as the primary method of storing genetic information, while ribonucleic acid is used mostly as a messenger molecule. RNA can form a cyclic intermediate with the 3’ phosphate of one nucleotide and the 2’ hydroxyl group, which makes it far easier to break apart. DNA cannot form a cyclic intermediate since it has no 2’ hydroxyl group – the mechanism for decomposing DNA is far slower. Therefore DNA (in the absence of enzymes) can last millions of years, while RNA breaks down much more quickly.
If one were to take a bunch of free nucleotides and dump them in a beaker and let them react, you would find that they will bind at each end, as well as at other orientations, such as on the parts of the base (the A, G, C or T part). If you had RNA, some reactions would even occur at the -OH group on the ribose that is missing in DNA.
The reason why, biologically, DNA is formed in one direction and not the other is because of the enzymes used. DNA (and RNA) polymerases only work in one direction, because, frankly, that’s all it needs to do. Why mess with something that already works? In the event of DNA damage leading to an exposed 5’ end somewhere on the helix, some polymerases but likely a ligase enzyme can come along and reattach it at that end, but these enzymes don’t have the ability to make long chains in that direction.
Find a biochemistry textbook and look up DNA replication - you’ll find that by necessity, one chain IS made backwards…the polymerase must make short segements of DNA going one way, and ligase follows along behind it and ties it all up together. It actually is a pretty fascinating mechanism.
As for WHY the enzymes work as they do…well, they are coded in the DNA, and if you think long and hard about it, you’ll find a nice “chicken and egg” situation
To the best of my knowledge, it would not be impossible to build a 3’->5’ polymerase, but that is not really how evolution works. Obviously, the first polymerase made was a 5’->3’ polymerase, and it has proven easier to evolve by duplicating and modifying it without chaging the core enzyme activity. No enzyme has come along to do the opposite, and with double stranded DNA replication figured out so neatly, I can’t think of a purpose for such an enzyme. It is always possible, though – nobody thought the RNA->DNA transformation step was possible until David Baltimore discovered reverse transcriptase.
I will check by biological physical chem textbook when I get to work, but in biology, in general, we can’t answer many of these “why” questions with any type of certainty. It is the same thing in why most amino acids are the L- stereoisomer, why rATP is used as a the main energy currency in metabolism while rGTP is used extensively in protein synthesis. I can’t remember any uses for rCTP or rUTP but they are probably used in another biological pathway.
thx for the replies. so…the polymerase restricts that operation. hmm…i guess the chicken and egg qns will not be so impossible if we dont treat them as “chickens” and “eggs” but rather as chemical congregations.
