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Thread: How are DNA nucleotides generated

  1. #1 How are DNA nucleotides generated 
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    The chromosomes are replicated in Synthesis part of cell cycle Interphase.
    About 204 billion atoms are required to complement the two sides of the human genome.

    How and where are the molecules (Adenine, Cytosine, Guanine, Thymine) generated?

    Does the cell know in advance that there are sufficient materials available?
    Are the materials stored in the cell (needed for transcription also)?
    If yes, as atoms or molecules?


    George


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  3. #2  
    Forum Cosmic Wizard i_feel_tiredsleepy's Avatar
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    Nucleotides are usually hanging around in substantial amounts as mono, di, and tri phosphates like GTP or ATP. Most organisms, including humans, can synthesise nucleotides de novo from basic amino acids. There is usually a build up of nucleotide synthesis early during cell replication which is probably turned on by the same signals that activate the cell cycle.


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  4. #3  
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    Thanks for your reply.

    If I understand correctly, you mention two sources of nucleotides:
    (1) from materials that "are usually hanging around in substantial amounts as mono, di, and tri phosphates like GTP or ATP."
    (2) synthesise nucleotides de novo from basic amino acids
    --------------------

    Is one of these a primary source and the other a secondary?

    DNA replication follows mitosis, another complicated procedure that replicates components in the cytoplasm. You're saying that "substantial amounts of GTP or ATP" and amino acids are available in the newly formed daughter cell?

    In either case, you indicate chemical changes must be done; the ACGT molecules are not stored as such?

    I assume these changes occur in the cytoplasm.
    Any idea what proteins or whatever are called upon to make the changes?
    (1) from GTP or ATP
    (2) from amino acids

    And what mechanism delivers each ACGT molecule as needed to the nucleus?

    Thanks for any comments.

    ps. If anybody knows of a book or web page that explains these matters, please let me know.
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    Forum Professor Zwirko's Avatar
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    A decent overview of nucleotide metabolism can be found here

    Also note that nucleic acids in the diet can be used and that nucleic acids and their precursors are also recycled by very important "salvage" pathways.

    My sister's son has no HGPRT enzyme (which is involved in purine nucleotide salvage) resulting in the very rare Lesch-Nyhan Syndrome - an example of something that go wrong with nucleotide metabolism.
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  6. #5  
    Forum Cosmic Wizard i_feel_tiredsleepy's Avatar
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    Thanks Zwirko, I had originally intended to mention salvage and had written a big long detailed post that got lost. I was at work so I had to result to that little short post after.

    @gs

    ATP and GTP are nucleosides they can be added directly onto a growing DNA chain. We have a lot of these molecules around in the cell because they are major components of enzymes, while ATP is the primary source of energy within the cell.

    http://upload.wikimedia.org/wikipedi..._structure.svg

    Take a look at the adenine nucleotide inside DNA, and then look at a ATP and you will see that they are very similar molecules:

    http://upload.wikimedia.org/wikipedi..._structure.svg

    As to the cell cycle, yes it is very complicated and frankly I would have to do a substantial bit of research to try and find specific answers about nucleotide synthesis during DNA replication. There are a few steps during the cell cycle called "checkpoints" where if certain things aren't present the cell division will be aborted (unless something is wrong with the regulation of the cell cycle in which case you have cancer). Essentially, the cell knows to build up nucleotides from amino acids/environment as well as amino acids themselves, sugar, extra ATP, ribosomes, and all the other stuff the daughter cells will need after division. A quick wikipedia search tells me that the enzymes used in DNA replication are upregulated in the G1 of the cell cycle, this probably includes enzymes in the nucleotide synthesis pathways.

    As to delivery to the nucleus, the nuclear membrane is highly permeable and really only stop large bulky things like proteins and RNA. Nucleotides are small enough to diffuse in.

    An intermediate biochemistry text on macromolecules should be able to answer any questions on these pathways.[img][/img]
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