Zinc fingers and oxidative DNA damage

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    Damage Dna Zinc
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Discussion Overview

The discussion revolves around the potential use of zinc fingers in addressing oxidative DNA damage, exploring theoretical applications in gene correction and repair mechanisms. Participants raise questions about the efficacy of zinc fingers, the role of nanoparticles, and various DNA repair strategies, including enzymatic and non-enzymatic methods.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested
  • Conceptual clarification

Main Points Raised

  • Some participants propose that zinc fingers could theoretically solve the oxidative DNA damage problem by correcting defective genes through homologous recombination.
  • Others question whether zinc fingers alone would be sufficient to address oxidative DNA damage or if additional methods, such as nanoparticles, could enhance targeting.
  • There are inquiries about the effectiveness of non-enzymatic DNA repair in conjunction with overexpressed DNA damage enzymes and whether this could mitigate oxidative damage.
  • Participants discuss the possibility of overexpressing DNA repair enzymes and the implications this may have on mismatched bases in DNA.
  • Some raise concerns about the potential for increased mismatched bases resulting from overexpression of repair enzymes.
  • Questions are posed regarding the ability of binding ligands to directly repair DNA and their hypothetical advantages over natural enzymes in recognizing mismatched bases.
  • There is a suggestion that while laboratory conditions may allow for certain repairs, translating these findings into therapeutic applications for humans may present challenges.

Areas of Agreement / Disagreement

Participants express a range of views on the effectiveness of zinc fingers and other repair strategies, indicating that multiple competing perspectives remain without a clear consensus on the best approach to address oxidative DNA damage.

Contextual Notes

Some discussions highlight limitations in current understanding, such as the dependence on specific conditions for successful gene repair and the unresolved nature of the relationship between enzyme overexpression and mismatched bases.

bioquest
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Can zinc fingers be used to solve the oxidative DNA damage problem? theoretically?
Scientists are closing in on techniques that could let them safely repair almost any defective gene in a patient, opening the door for the first time to treatments for a range of genetic disorders that are now considered incurable.
The breakthrough, announced in the journal Nature in June, relies on so-called zinc fingers, named after wispy amino acid protuberances that emanate from a single zinc ion. When inserted into human cells, the fingers automatically bind to miscoded strands of DNA, spurring the body's innate repair mechanism to recode the problem area with the correct gene sequence.
"By attaching zinc fingers which determine where transcription factors bind to endonuclease, which break DNA strands, homologous recombination can be induced to correct & replace defective/undesired DNA sequences"
 
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Biology news on Phys.org
This is from http://www.wired.com/medtech/health/news/2005/07/68019 except for the last quote I need to find out where I got the last quote from. I don't see the edit button sorry I forgot about the copyright rule
 
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bioquest said:
This is from http://www.wired.com/medtech/health/news/2005/07/68019 except for the last quote I need to find out where I got the last quote from. I don't see the edit button sorry I forgot about the copyright rule

I just shortened the quoted part above now that you have provided the link to the full article for people to follow.
 
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Okay...do you think zinc fingers could make it so that oxidative DNA damage is no longer a problem, though?
 
I mean if they were used for gene correction, *could* zinc fingers solve the oxidative DNA damage problem? why/why not?
 
I mean could nanoparticles or something be used to help the zinc fingers target genes?
 
Would zinc fingers only help with fixing DNA through homologous recombination?
 
Um ignore all my other questions but I did have these so if you answered them that would be appreciated

Could non-enzymatic DNA repair (In combination with overexpressed DNA damage enzymes or something) solve the oxidative DNA damage problem? Why/why not?

Also is phenylpropanoid glycoside enzymatic or non enzymatic DNA repair?

And does DNA repair that's not in non-homologous places always require healthy undamaged DNA to be able to fix oxidative damage?
 
What repairs the DNA when an incorrect base is inserted? Is there something that can/will always be used to do that ie if it's overexpressed or something?
 
  • #10
it won't let me edit, but

I thought they made nanochips or something that allow you to look inside cells? Could you look inside the cells, and as a result be able to correct bases that are incorrect in cells?
 
  • #11
This is my only question, you can ignore all the other ones, sorry I can't delete the other ones

Would there be a way to overexpress DNA repair enzymes to solve the oxidative DNA problem (or solve it as much as possible) in a way that wouldn't result in more problems with mismatched bases as a result of that?

Could binding ligands here http://old.iupac.org/news/prize/2002/sando.html be used to directly repair DNA? Could mismatch binding ligands here recognize mismatched bases better than our own natural enzymes in any way, hypothetically, if so in what ways? thanks
 
  • #12
never mind the question about the ligands my question is just about overexpression and mismatched bases (the questions in the above post) thanks I really appreciate the answer
 
  • #13
bioquest said:
Would there be a way to overexpress DNA repair enzymes to solve the oxidative DNA problem (or solve it as much as possible) in a way that wouldn't result in more problems with mismatched bases as a result of that?

Possibly. Even if it's achieved under laboratory conditions, it's not quite the same as bringing a therapeutic product to market which needs to be validated for regular use in humans.

It's hard to say without more research and testing. Has there been any followup work by the authors and/or company mentioned in the article?
 
  • #14
I don't remember where I read that overexpressing DNA damage repair enzymes causes a higher amount of mismatched bases but my perception at the moment is that they do
 

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