Talk:DNA repair

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Ideas welcome!

prometheus1 12:47, 10 Aug 2004 (UTC)

I'm working on reorganizing the sentences, to make them shorter and more understandable, and adding more links. I have translated some Bioinformatics books, but I'm by no means fluent in this field, so I'll not touch the contents. Hope it's okay with you. :-) -- Autrijus 04:04, 14 Aug 2004 (UTC)

Delighted to have your assistance. prometheus1 07:40, 15 Aug 2004 (UTC)

Contents 1 Copyright notice on images 2 DNA damage 3 Caloric restriction increases DNA repair 4 DNA repair mechanisms:mammalian cells 5 'Not commonly known' 6 double strand damage and dna repair 7 References 8 Junk DNA 9 Interstrand crosslinks 10 FARC and such 11 DNA repair evolution 12 Revisions

[edit] Copyright notice on images

Putting the fact that they're non-commercial use only aside, it's really bad style to have the copyright notice directly in the picture. It implicitly discourages reuse of the image, which goes against Wikipedia policy. 07:31, 16 Aug 2004 (UTC)

Sorry John, but I created these images specifically for the DNA repair article (you will not find anything similar anywhere else) and my preference is that they not be used outside this context. prometheus1 14:43, 16 Aug 2004 (UTC)

How about a compromise where you put "(c) Prometheus for Wikipedia" or something similar? Or might that be too long? You could always watermark the picture if you were worried about image propagation etc.

[edit] DNA damage

I think there are a couple of things that could be clarified here.

1. I get the sense that 'molecular lesion' as a more precise meaning than given in either the earlier link to lesion or the link to molecule here. A link to a stub on 'molecular lesion' would be a good idea.
   • good idea prometheus1 23:18, 24 Aug 2004 (UTC)
2. I take it the molecules under discussion are chromosomes and these rates are estimated with respect to the sum of all chromosomes in the nucleus (although there is a reference to mitochondrial DNA later. (Oh boy and the mitochondrial DNA article needs a good clean up))
   • If you check with the DNA article before proceeding with this one then you get sufficient background on the DNA molecule - but you are correct - the higher order of DNA takes the form of chromosomes which also include histone proteins, whereas the mitochondrial DNA structure resembles that of a bacterium prometheus1 23:18, 24 Aug 2004 (UTC)

   What I'm thinking is that any estimate of the number of 'molecular lesions per cell per day' is going to depend on the number of DNA molecules in the cell and the size of those molecules. This can vary by a couple of orders of magnitude between a nematode worm and a polyploid plant like wheat. Of course, there is probably also a difference in the damage rates, so if these numbers are based on the human cell, this ought to be mentioned. -- Solipsist 00:10, 25 Aug 2004 (UTC)

3. We are implicitly talking about human DNA and the molecular lesion rate would be lower in a fruit fly (although later there is a reference to Mammalian cells).
   • let me know of any specific ambiguity and I'll rewrite it prometheus1 23:18, 24 Aug 2004 (UTC)
4. Assuming I've guessed these points right, it would be useful to put the lesion rate into context of the 3.5bn nucleotides of human DNA
   • good idea, it helps put things in perspective prometheus1 23:18, 24 Aug 2004 (UTC)

Some of these things can be infered from later portions of the article, but aren't obvious at this point. -- Solipsist 08:50, 24 Aug 2004 (UTC)

[edit] Caloric restriction increases DNA repair

I'm kinda thinking that the caloric restriction section should be either

1. taken out
2. moved to it's own entry, or
3. it's relation to DNA repair should be explained more explicitly.

I say this because its connection to DNA repair as it stands seems really sketchy and the caloric restriction section seems kinda thrown in.

But, I'm hesitant to take out an entire section. Any feedback?

Harvestgalaxy 05:44, 15 Sep 2004 (UTC)

provided some clarification - is this ok? prometheus1

[edit] DNA repair mechanisms:mammalian cells

"Mammalian cells cannot tolerate DNA damage as it interferes with the integrity and accessibility of the information encoded in the genome"

Why is this statement addressed to mammalian cells in particular? Can reptilian, avian cells etc. tolerate DNA damage better than those of mammals? If this is not the case, that comment should be deleted or rephrased. If it is indeed the case can someone more knowledgeable try to elaborate?

[edit] 'Not commonly known'

What does this sentence mean?

'Diseases not commonly known to be associated with reduced DNA repair function include Fanconi's anemia, hereditary breast cancer and hereditary colon cancer.'

Axl 11:29, 12 Nov 2004 (UTC)

good point prometheus1

[edit] double strand damage and dna repair

There are some inaccuracies in the articles about damage and repair. I have made a change to the double strand damage section renaming it "double strand breaks" since damage such as oxidized bases opposite each other are not in themsleves repaired by recombination but must first be turned into a double strand breaks. This creates some incompatibility with the picture provided showing base damage on both strands which appears to have been added to distinguish single versus double strand damage, and I am not sure what to do about it. I believe it will require further editing to distinguish damage which results in chemical changes to the DNA without breaking it, and strand breaks.

Single strand breaks are incredibley numerous and are rapidly repaired in the cell by religation dependant on XRCC1. This probably requires a mention seperate from the other single strand damage repair mechanisms mentioned.

Also perhaps deserving a seperate mention is trancription coupled NER.

Finally, there is a statement that replicating cells have an additional repair pathway dependant on polymerases. This is misleading. DNA replication of damage creates mutations and repairs nothing. They only allow tolerance of the damage. Repair polymerases are used as part of all the DNA damage repair mechanisms mentioned in the article and are not dependant on the cells dividing and so I believe this statement should be removed entirely. --Harrison35 04:40, 3 Feb 2005 (UTC)

[edit] References

Hi, I am working to encourage implementation of the goals of the Wikipedia:Verifiability policy. Part of that is to make sure articles cite their sources. This is particularly important for featured articles, since they are a prominent part of Wikipedia. The Fact and Reference Check Project has more information. Thank you, and please leave me a message when you have added a few references to the article. - Taxman 18:52, Apr 21, 2005 (UTC)

[edit] Junk DNA

Here is the quote that I have a question about: "the so-called "junk DNA", this mutagenic repair is less likely to be harmful to a cell than homologous recombination with sequences other than the sister chromatid."

Based on the most recent evidence on how the so called junk DNA is actually useful for putting together various segments of RNA to make proteins, can this sentence still be maintained on the page? Can someone knowledgeable comment on this please?

--PiKeeper 14:36, 26 October 2005 (UTC)

You're most correct. I will be undertaking a rewrite of this article over the next few weeks to bring up the level of accuracy and ensure that it's properly referenced. Cheers. prometheus1 09:52, 4 December 2005 (UTC)

[edit] Interstrand crosslinks

Interstrand crosslinks and what is know of their repair (FA-pathway) might possibly be added.

[edit] FARC and such

I don't know if anyone else is watching this article, or (better yet) if any of the original creators are still around. I am somewhat concerned about the two pathway images that appear in the article. The first (dnarepair1) refers to senescence as a consequence of pathology, which is true in a strict sense, but senescence is still a normal, not-necessarily-pathological process. For the second (dnadamage), I haven't been able to verify all the effector relationships shown. If anyone has/knows of the original references, that would be very useful. Opabinia regalis 06:14, 26 May 2006 (UTC)

I am watching it now. Feel free to contact the original editors! - Samsara (talk • contribs) 13:15, 26 May 2006 (UTC)

Well, since the primary author prometheus1 hasn't been around since 2005, I don't think he's going to see the changes or the note I left on his talk page.

Are there any content concerns aside from the references? Opabinia regalis 20:09, 26 May 2006 (UTC)

It's great that you've taken the time to supplement the references and reduce the amount of bullet-pointing in the article. However, I'm concerned that large chunks of material towards the end of the article have been removed without justification. I think some of those can be supported with references, even from other articles on Wikipedia; in fact, those articles should probably be linked together more closely (e.g. calorific restruction). - Samsara (talk • contribs) 17:50, 27 May 2006 (UTC)

Honestly, the end sections in the original version were rather redundant, and contained a few inaccuracies (some due to new data since the first writing). The connection between aging and DNA repair was made repeatedly. Recent data suggests that antioxidants don't correlate well with longevity (eg this paper), so I removed that claim. I also removed the claim that DNA repair and rate of evolution are inversely correlated, as evolution rates are a function of both mutation and selection.

The statement that DNA repair mechanisms evolved during the pre-Cambrian in response to the emergence of an oxygen atmosphere was removed due to being trivially true and uninformative (the "pre-Cambrian" period covering everything in Earth's history up to the Cambrian, at which point multicellular eukaryotes were established) and because there's no specific reason DNA repair would not have existed even before an oxygen atmosphere. Radiation damage and sloppy replication would still have existed prior to the oxygen transition. Anaerobic bacteria have DNA repair machinery despite not being adapted to an oxygen atmosphere. Pubmed turns up nothing for "DNA repair pre-Cambrian" with or without the hyphen, and the top Google hits are Wikipedia mirrors. (And CreationWiki, but let's not count them.)

The "gene therapy" section had little content, and what was there is best covered under a gene therapy topic. Most genes "are able to alter the amount of protein they produce based on changing cellular conditions" and I've never seen the phrase "smart genes" used outside of marketing hype. The smart genes wiki page references are about biological automata.

I've rearranged the order of the sections a bit and added a separate section for caloric restriction information as it relates to DNA repair, but CR does have a lengthy article of its own already. Opabinia regalis 01:36, 28 May 2006 (UTC)

Thanks for the detailed explanations. As long as any content that is better covered by other articles is linked to, I'm basically happy. - Samsara (talk • contribs) 09:04, 28 May 2006 (UTC)

For completeness' sake, I've added a link to gene therapy in the "See also" section. Opabinia regalis 02:14, 29 May 2006 (UTC)

Great work - made some amendements and added some refs - check it out --prometheus1 08:23, 3 June 2006 (UTC)

[edit] DNA repair evolution

Thanks prometheus1 - glad you're back! You wrote a very cool article here and it's great that it made it to featured status. Thanks especially for simplifying the lead.

I do still have some reservations about the descriptions you've added in the evolution section, but perhaps you can convince me I'm wrong - this is a bit out of my field. Saying that DNA repair evolved "at least as early as the Precambrian" is not informative, as the Precambrian is defined to have begun with the Earth's formation (and this is the usage upheld by the wiki article on the topic) - so unless you're implicitly acknowledging the possibility of panspermia, in which case the possibility ought to be stated explicitly, DNA repair could not possibly have evolved any earlier. The fact that multicellular eukaryotes were well established by the beginning of the Cambrian also makes clear that DNA repair was obviously much earlier. I'm not aware of literature that makes an estimate for the age of the first DNA repair systems, but maybe you've seen something that could pin it down more specifically to a time period within the Precambrian?

I also question the implication that most or all forms of DNA repair are related to/responses to the oxygenation of the Earth's atmosphere, for the reasons I outlined above. Radiation damage and poor replication would have provided impetus for DNA repair mechanisms even in the absence of oxidative damage, and today's anaerobic bacteria maintain DNA repair systems without being adapted to the use of oxygen in metabolism.

My last minor quibble, which I bring up here only because I just made the change, is with the title of the last subsection "DNA repair rate as a function of evolutionary rate", when the text suggests the opposite, that the rate of evolution is a function of DNA repair rate by virtue of being a function of mutation. Of course this is a give-and-take situation, but in context I think it's clearer the other way around. Opabinia regalis 06:23, 6 June 2006 (UTC)

It is fairly well accepted that during the precabrian period a variety of microorganisms proliferated including cyanobacteria and the first eukaryotes (do a pubmed search using "precambrian" as the search term). In consideration that DNA repair mechanisms have been identified to exist and be conserved in bacteriophages -- evolutionarily more primitive than bacteria -- it is a reasonable assumption that at this time of single celled organism diversity that DNA repair mechanisms also existed. In fact, any genetic construct that requires a certain degree of resistance against environmental factors that would destabilize it requires some compensatory strategy of repair. The informational redundancy of the double helix provides a template for repair from damage that could be effected by polymerases associated with duplication. Therefore it would only require a slight adaptation of a duplication polymerase to enable it to function as a DNA repair enzyme. I'm fairly sure that I came across the reference to the precambrian period as an origin to DNA repair in the 1995 edition of "DNA repair and Mutagenesis". Unfortunately I have since lost the textbook but as of this entry I placed an order for the second edition which came out in 2005. In relation to oxidative damage it is also recognised that reactive oxygen species (ROS) are the most important contributors of DNA damage. As for DNA repair vs evolutionary rate you're right - my snafu. Cheers.

--prometheus1 14:56, 6 June 2006 (UTC)

Maybe I'm being nitpicky, but the fact that the Precambrian is such an enormous span of time makes the statement "DNA repair evolved during the Precambrian" essentially equivalent to "DNA repair evolved sometime between the Earth's formation and the establishment of multicellular eukaryotes", which sounds like a handwaving way of saying "We have no idea exactly." I'm not questioning the truth of the claim; I'm saying it's sort of trivially true. Worse, saying "At least as early as the Precambrian" implies that it could have been earlier, which is impossible unless life originally evolved elsewhere besides Earth. So a more specific time period during the Precambrian would be useful; unfortunately I haven't come across any literature willing to make a guess. I agree, though, that it was probably very soon after the emergence of polymerases, and polymerases were probably among the first functional proteins.

The point about oxidative damage is admittedly nitpicky - ROS may be the largest source of DNA damage now, but surely something like a photolyase or other thyime-dimer-reversal mechanism could have come much earlier than the oxygen atmosphere.

At any rate, I've reorganized that section a bit; take a look to see if it's still consistent with your view of the matter. Opabinia regalis 01:42, 7 June 2006 (UTC)

Marvelous! I think it would be sensble to also include your points on other sources of DNA damage.

--60.230.44.60 02:30, 7 June 2006 (UTC)

That was me by the way, I forgot to sign in. I'll work on the obtaining the references for the diagram next but it may take a while.

--prometheus1 02:32, 7 June 2006 (UTC)

Awesome. I added some clarification about responses to oxidative damage and also reorganized the DNA damage section a bit. Thinking about it, it seemed odd to have the senescence and mtDNA stuff before the discussion of DNA damage itself. Opabinia regalis 04:16, 9 June 2006 (UTC)

[edit] Revisions

Is anybody interested in my expertise, which is nucleotide excision repair (and DNA repair)? I don't see much I can add to the DNA repair article but the NER is very sketchy, and eukaryotic NER is nonexistent. Maybe I can add some stuff there? (I raise the questions here as people seem to follow this page while there is no such thing at the NER page). Cheers Marvol 17:39, 15 August 2006 (UTC) BTW in case you wonder about my credentials, I did my PhD on human NER :-)

That would be great! The best thing to do is probably to just go ahead and start expanding/improving upon the nucleotide excision repair article, which as you noticed is rather lacking at the moment, and any related subjects you find interesting. I kind of have an ongoing project expanding our coverage of proteins and protein folds, so if you feel so inclined I think articles on the enzymes in eukaryotic NER would be nice :) Opabinia regalis 23:53, 15 August 2006 (UTC)

There is no way that there are more than 1 million lesions per cell per day. There are ~10,000 depurinations, ~2,000 oxidative lesions, ~80 cytosine deaminations. These are the major forms of damage.

I agree with Marvol that major revisions are needed here. I am teaching a an advanced graduate level class in DNA Repair and Mutagenesis this Fall and I would like to have my students edit this section as a term project. Each student will edit a different section. We will be using the new edition of the Errol Friedberg book "DNa Repair and Mutagenesis" and research literature for the class, and hence we should be able to make it quite upto date. How about it? Asbhagwat 03:14, 19 August 2006 (UTC)asbhagwat

I'm looking at the reference for the 1,000-1,000,000 number, which is a general cell bio text. In an excellent argument for inline citations, the book does not specifically footnote its references and it's unlikely I will go through the 20 or so papers listed, so I don't have the primary citation. That estimate could well be out of date. Where did your numbers come from?

Students editing articles for a class seems to happen fairly frequently, and especially advanced students are always welcome. A suggestion would be to make sure they're familiar with wiki markup and the referencing system first, since neither scheme is really used outside of wikis. Also be aware that very long articles tend to be discouraged, so if they end up with large amounts of material for a particular section, you might think about creating separate articles for those subjects, or asking the students to contribute to some of the sub-articles. (As Marvol pointed out, the articles on specific types of DNA repair are very stubby and could use some expert attention). Opabinia regalis 04:03, 19 August 2006 (UTC)

The numbers I provided are fairly standard. Look for example- ) “DNA Repair and Mutagenesis” by Friedberg, E. et al (2006) ASM Press, Second edition, ISBN #1-55581-319-4. Table 2-1. All of these are estimates based on known properties of DNA. If you need a research publication, see Lindahl, T. (1993) Nature 362: 709-715. Asbhagwat 22:19, 21 September 2006 (UTC)

I am going to edit this page to update various aspects of DNA repair. How do I change the "Contents"? They are too skewed towards aging and diet related issues. I would like to update with oxidation of DNA methylation, excision repair and mismatch repair. Also, I would like to discuss human genetic diseases caused by defects in DNA repair. Asbhagwat 04:11, 1 November 2006 (UTC)

Great! The table of contents will update itself automatically - each header line surrounded by "==" on both sides of the text appears as a top-level heading in the table of contents. (Subsection headers are marked with "===" and so forth.) Awhile ago I shoveled a large amount of aging-related stuff out of this article, but it still looks lopsided. Your suggested additions would be very useful. Opabinia regalis 06:57, 1 November 2006 (UTC)

While things are being revised, it would be helpful if someone would look at all of the headers. The MoS:HEAD guideline states that the article title, DNA repair, should typically not appear in the headers. JonHarder 23:44, 1 November 2006 (UTC)