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DNA damage repair enzymes

  1. Aug 10, 2008 #1
    Are there any known enzymes that will fix oxidative dna damage without correcting mismatched bases? Any enzymes that are thought to work like that? thanks
  2. jcsd
  3. Aug 10, 2008 #2


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    Yes. Photolyase is one such example that fixes thymine dimers (by using the energy from light which creates thymine dimers in the first place. Pretty cool!). Another example is 8-oxoguanine glycosylase which repairs oxidized guanine nucleotides. I'm sure there are other examples, but these are the first two on the top of my head.
  4. Aug 11, 2008 #3
    well I read that

    Photolyase is present and functional in prokaryotes, is present in lower eukaryotes (as yeast) where it is thought to have a minor role, and it has not been found in human cells. However, many higher eukaryotes, including humans, possess a homologous protein called cryptochrome that is involved in light-sensitive regulatory activities such as modulating circadian rhythms.

    but even though it's not found in human cells it could be introduced into them, through genetic manipulation or endosomes or something right, I mean could it be?
    Last edited: Aug 11, 2008
  5. Aug 11, 2008 #4


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    Probably. You'd probably have to modify the enzyme to tell human cells to send the protein into the nucleus (remember prokaryotes have no nucleus so they lack nuclear localization signals that target them to the nucleus), but in theory there should be nothing that would prevent you from getting these proteins to work in humans.
  6. Aug 11, 2008 #5
    I know photolyse won't work; What are the other enzymes that would fix oxidative damage but not mismatched bases? 8-oxoguanine glycosylase can't fix all the oxidative dna damage right?
    Last edited: Aug 11, 2008
  7. Aug 11, 2008 #6
    8-oxoguanine glycosylase is a member of the larger DNA glycosylase family, which contains a number of related enzymes that do similar chemistry on different base pairs. There's even a uracil-DNA glycosylase, which sounded a bit strange to my ear the first time I heard of it, but it does exist.

    Nucleotide excision repair (a more general and flexible alternative to more specific DNA repair mechanisms, as I recall) involves a number of proteins in eukaryotes, of which I can remember about two, if I'm lucky, on a good day. You may be interested in investigating that more carefully, as I am of no use on the subject.
    Last edited: Aug 11, 2008
  8. Aug 12, 2008 #7
    what about the enzymes in this plant 4767-year-old bristlecone pine although I heard some of the cells in it were only a couple of years old
  9. Aug 12, 2008 #8
    okay I just realized only the bark was alive in that plant or something/that I was misinformed but

    Anyone have insight on what DNA repair enzymes/systems you would add to something to extend it's longevity/help with aging. overexpressing some of them seemed to cause more problems with mismatched bases, so I wanted to know about potential non human dna repair enzymes/systems that could be added to a mouse
  10. Aug 12, 2008 #9
    Many of these mechanisms are found in a number of organisms across all domains of life. They are not exactly the same, of course - for instance, nucleotide excision repair (NER) in eukaryotes involves more proteins than in prokaryotes - but the basic notion of NER is conserved.

    I'm not aware of anyone trying to add a completely new DNA repair pathway to an organism, but DNA repair research is a rather large world to keep track of, especially if you're not in the field (such as myself). You might find the DNA Repair Lectures site at the Roswell Park Cancer Institute useful as a starting point for navigating through the field. I would suggest starting with the references there, at least with regard to finding people who are currently involved with the cutting edge research and go from there.

    Good luck!
  11. Aug 14, 2008 #10
    Does photolyse fix oxidative dna damage?
  12. Aug 14, 2008 #11
    The links provided have very clear explanations of what photolyase does, far more so than what someone who is not a specialist (aka me) can provide. The page on direct repair of DNA damage on the Roswell Park website mentions something that is of relevance to your earlier question about introducing a foreign photolyase to an organism. It takes a simple Google search to find the (freely available) paper which discusses the answer to this question.

    I get the impression that we're being asked to spoon-feed homework answers. It may be uncouth to say so, but I can't shake the feeling.....
  13. Aug 14, 2008 #12
    well but what I mean is, could photolyse solve the oxidative dna damage problem, or would it only fix some of the damage? I'm not in school yet so its not homework answers I mean I know it's called the homework help forums
  14. Aug 14, 2008 #13


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    There are many types of oxidative damage that can occur on DNA. As such, there are many enzymes to recognize and fix oxidative damage. Photolyase will fix only a certain type of oxidative DNA damage (thymine dimers) and will not fix other types.
  15. Aug 15, 2008 #14
    Is there any known one enzyme that would repair all oxidative dna damage/is there any known combination of enzymes that would solve the oxidative dna damage problem if overexpressed or something? (Without causing higher problems in mismatched bases) What are the ones, if any, that would do it without fixing or attempting to fix/making mistakes in fixing mismatched bases?

    Last edited: Aug 15, 2008
  16. Aug 15, 2008 #15
    Base excision repair mechanisms typically rely upon specific DNA glycosylases for proper functioning, so they're hardly an extremely general mechanism. The direct repair methods are usually only there for particular types of DNA damage (such as photolyase), so they will only revert back a particular sort of damage. Nucleotide excision repair relies upon structural perturbations to the DNA upon damage, so it's a bit more general, but it is not foolproof either. There are other mechanisms which come into play under certain circumstances, but are not otherwise active.

    There's no one single DNA repair mechanism that I'm aware of that can repair everything with the necessary fidelity to the original genome. This is why there are so many different systems -even mismatch repair - to overlap one another and make sure that your genes stay intact.
  17. Aug 15, 2008 #16
    Is there any known thing- any combination or anything of enzymes etc I say combination because you said "there's no one single DNA repair mechanism that can repair everything with the necessary fidelity to the original genome" that if overexpressed or something or just used the way it is would solve/almost solve or anything the oxidative dna problem? without creating a higher problem with mismatched bases? (Since apparently it would see problems that weren't there and try to fix what didn't need to be fixed) I mean I guess it could/would cause other problems I was just asking about the ones that wouldn't cause increased problems with mismatched bases

    I mean, are the answers to these no/unknown? with our current knowledge?

    So direct reversal methods wouldn't solve the oxidative dna damage problem or anything, they would just work on some types of oxidative damage?

    So there's not a group of enzymes, with for example something like photolyse in it, that could solve/mostly solve or anything the oxidative dna damage issue and not cause more problems with mismatched bases?
    Last edited: Aug 15, 2008
  18. Aug 15, 2008 #17
    From the little I've read since undergrad molecular biology, one would probably have to find a way to upregulate (overexpress) EVERY repair mechanism in order to ensure that adequate fidelity is ensured. The question is, given the baseline rate of mutations in eukaryotes (which is a value I don't remember), just how much upregulation would be required to suppress even that? If you need a huge jump in upregulation for a minimal effect in taking care of baseline mutation, it might not be worth it, which will make sense by the end of this post. I get the impression it could be one of those things where 10% effort will get you 90% of the desired results, but that last 10% of the desired results is extremely costly.

    Another issue is how to actually initiate DNA repair mechanisms. I know that people have suggested that there are redox chemistry-based triggers, triggers related to varying points of the cell cycle, interactions of other genes which end up providing a mechanism for initiating DNA repair....the question becomes, if one has to start messing around with the redox chemistry within the cell, or mucking around with the various biochemical events in the cell cycle, you might set off DNA repair at a higher rate, but at what cost to the rest of the cell?

    Direct repair methods reverse specific chemical (oxidative) modifications, they're not general ways of cleaning up DNA. Photolyase reverses the production of cyclobutane pyrimidine dimers. O6-alkylguanine alkyltransferase reverses the alkylation of guanine. They are not more general methods like the various types of excision repair pathways.

    There might be hints or even partial answers to potential questions to your answers, but they're probably strewn about in the research literature, alluded to but not really strongly asserted since it's too early to say. I did get curious about the idea of transplanting a foreign photolyase into mice - Google "mouse foreign photolyase" one of these days, and you'll find the paper which describes an experiment that did just that. What I've presented is pretty much the textbook knowledge of DNA repair (as that is all I am actually familiar with myself). It would make for an interesting literature review or even meta-analysis, though.
  19. Aug 15, 2008 #18
    it's only the enzymes, nothing else that repairs DNA right

    But when combined do the direct reversal methods reverse every type of oxidative dna damage? (When combined) or do they not cover all the types?

    If you overexpressed all the dna repair enzymes, and that caused a higher amount of incorrectly fixed mismatched bases, would the dna repair enzymes also eventually correct the mismatched bases? Or would the incorrectly fixed mismatched bases still be a big issues
    Last edited: Aug 15, 2008
  20. Aug 15, 2008 #19
    Well, it depends on the mechanism as to what does the work of DNA repair. For something like photolyase, it's just the photolyase as I recall - it breaks the bonds between the two pyrimidine bases, and that's pretty much all there is to say. But if you look at the nucleotide excision repair pathway (see here), there are a lot of proteins involved in the process. The base excision pathway (see here) makes note that you need the appropriate DNA N-glycosylase, followed by an AP endonuclease, followed by DNA polymerase to make the entire repair.

    My understanding is that the direct reversal methods are not able to reverse every type of oxidative damage. To quote the Roswell Park website,

    If that's being said about the base excision repair pathway (which uses DNA glycosylases), I would think it applies even more strongly in the case of direct DNA repair.

    As for your last two questions, not sure. Sounds like it would make for a good set of experiments, though, if they haven't already been done.
  21. Aug 15, 2008 #20
    Could/Would the increase of problems with mismatched bases etc caused by the enzymes be permanent- would they only be able to fix those errors after 2 generations/a limited amount of time or could they fix them anytime?

    is that known? My friend said they only repair mismatched bases after 2 cell generations or she said something like that indicating that after an amount of time has passed, they don't correct the mistake anymore, but maybe if all the enzymes were overexpressed they would eventually fix all the mistakes?
    Last edited: Aug 15, 2008
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