Homologous recombination is an important mechanism of DNA repair and is also a major engine of genetic diversity. I have worked intermittently on this article since December 2008, expanding it from a stub to its present state. The article has gone through two peer reviews, one before and one after a successful GA nomination. I believe it now meets the featured article criteria. Thanks in advance for any comments and suggestions. Emw (talk) 16:35, 13 June 2010 (UTC)[reply]
This will be a difficult article for many readers to understand and some will not read any further than the Lead. I would like to start my review with this section, which should be able to stand alone.
1. I know many sources use the expression "double-strand break" but I think it should be explained or not used in the Lead. Try something like "a break that occurs on both strands...."
I agree -- done.
2. Instead of "evolutionarily adapt", I offer "adapt during the course of evolution".
So changed.
3. I could not find the reference to horizontal gene transfer in the source cited. Perhaps I missed it.
Fixed. The reference was intended for the previous sentenced.
4. The 5' end usage could cause confusion. The expression "5' end of the damaged chromosome" is used, but chromosomes don't have 5' and 3' ends, they have both types at both ends. I have drawn a diagram to help other reviewers understand my point:Discussed in point 4. When DNA is damaged on both strands, new 5' and 3' ends are exposed. It is these newly exposed ends that are the subject of discussion here and not the "5' end of the chromosome". We need a better expression to identify the different strands.
Reply The usage could be misconstrued, but I can't think of a succinct clarification. I try to indicate which pair of 5' ends are cut away by putting things in context: "sections of DNA around the break on the 5' end of the damaged chromosome". That paragraph is an attempt to sum up the most important mechanistic details, and as such I think it will be the most challenging for readers.
I think "ends" (plural) would be better, perhaps "the 5' ends of the break" is better than chromosome here. I offer, After a double-strand break occurs, sections of DNA around the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the damaged chromosome then "invades" an undamaged homologous chromosome.Graham Colm (talk) 15:56, 17 June 2010 (UTC)[reply]
To help the situation I've considered trying to make a lead animation, perhaps something along the lines of the DBSR model here: http://web.mit.edu/engelward-lab/animations.htm. Do you think something like that could be appropriate?
5. Here, "they share some of the same steps" I think the same is redundant.
Agreed, fixed.
6. This statement bothers me "and has been observed in viruses, suggesting that it is a fundamental biological mechanism". Why does it? Given that viruses are highly evolved and highly efficient biological entities, the mechanisms that they use are not de facto fundamental.
Reply I was more trying to find some way to say "three domains and viruses" than to imply that HR is important because it's observed in viruses. I've attempted a fix. Also, on closer scrutiny the word "fundamental" seems vague; I've tried addressing this too.
Last for now, and this is not in the Lead but in the section on viruses, the use of Influenza was a poor choice because these viruses mix up their genes more often by reassortment, which if a different mechanism to the one described in this article. I will add more to this review during the next few days.Graham Colm (talk) 16:27, 16 June 2010 (UTC)[reply]
Many thanks for your thoughts so far! They're very helpful. And good point on the influenza example. I will work tonight to fix that and find better examples. Emw (talk) 00:13, 17 June 2010 (UTC)[reply]
There's formatting problem with reference 41, and this paper also by Eddie Holmes might be a useful citation for this section:[2]. Also, it will greatly help the closing delegate if you could clearly distinguish your replies from my comments. Signing each reply is probably the easiest way :-) Graham Colm (talk) 15:56, 17 June 2010 (UTC)[reply]
More comments
I think the section on Eukaryotes should come before Bacteria. It seems a more logical structure to me and some readers might find the Bacteria section difficult and the beginning of the Eukaryotes section is gentler in this regard. The Bacteria section also introduces single-strand breaks for the first time—the reader has not be introduced to these in the Lead, so I think a sentence or two about these in the Lead is needed. Another problem with the Lead is that it discusses DNA only, but the section on viruses also discusses RNA, again I think a sentence needs to be added to the Lead. Graham Colm (talk)
I've switched 'In eukaryotes' and 'In bacteria'. I changed 'single-strand break' to 'single-strand gap' as the latter seems to be used more in literature, and also added an appositive to the first instance of the term in the first paragraph of 'In bacteria'. Tomorrow I will make any adjustments to the lead regarding single-strand gaps and RNA. Emw (talk) 04:47, 18 June 2010 (UTC)[reply]
This needs a source, " Left unrepaired, these double-strand breaks...can in turn lead to cancer."Graham Colm (talk)
Although it can stand on its own as a static image, this figure is intended to be viewed as an animation. The extra white space on the bottom allows the depicted DNA molecule to be centered while the frames are carried out. If cropping out the white space de-centered the DNA in the animation, would you still prefer it to be cropped? Emw (talk) 04:47, 18 June 2010 (UTC)[reply]
I think a short section on the history of HR research would improve the article by putting the subject in a context that will help readers new to the subject. I suggest something along the lines of: Following on from the discoveries made by Gregor Mendel, it was shown that genes are often linked and do not segregate randomly. This was discovered by William Bateson and Reginald Punnett who were pioneers in the field of genetics during the early 1900s. In 1911, Thomas Hunt Morgan introduced the term "crossing over" and it was shown later that this occurred by an exchange of material between pairs of chromosomes during meiosis. Curt Stern later showed that crossing over—later called "recombination"—could also occur during mitosis. In 1930, Hans Winkler—who coined the word "genome"—introduced the term "gene conversion". The discovery of the structure of DNA in 1953 by James Watson and Francis Crick, and work on mutants of bacteria led Robin Holliday, in 1964, to propose a model for homologous recombination in meosis now called a Holliday junction. Graham Colm (talk) 17:07, 17 June 2010 (UTC)[reply]
Excellent idea, and thank you for the suggested wording. I've added a two-paragraph 'History and discovery' section, with references. The first paragraph is taken directly from your suggestion. The second paragraph attempts to link those historical studies with models of recombination discussed in the article. Emw (talk) 06:43, 22 June 2010 (UTC)[reply]
I am very concerned about the depth of detail in the article, which is deeper than the current textbooks that I have next to me. I think this level of detail, with its unavoidable jargon, is too much for an encyclopedia. Much of this article will not be understood by readers who lack highly specialist knowledge. I think the article needs to be written as more of an overview rather than a scientific review. The descriptions of HR in the books I have before me (Lewin's Genes X, 2011, ISBN9780763779924, Molecular Biology-genes to proteins, 2008, ISBN9780763759636 and Lewin's cells, 2011, ISBN9780763782665) are much clearer. I would be interested to hear the views of other reviewers on this.Graham Colm (talk) 21:27, 17 June 2010 (UTC)[reply]
The depth of the most involved parts of this article is about on par and in many places less detailed than textbooks I have consulted. These include Albert et al (2008) Molecular Biology of the Cell, 5th edition; Lehninger (2005) Principles of Biochemistry, 4th edition; and Friedburg et al (2009) DNA Repair and Mutagenesis, 2nd edition. Compared with other featured articles on specific subjects in molecular biology, for example RNAi and Exosome complex, I don't think this article is more difficult to read. I think this article does a notably better job than those in introducing readers to technical terms, even before your helpful notes on what jargon could use more explanation. Also, I would note that I've preempted the two peer reviews for this article (first, second) asking reviewers to pay special attention to the issue of this article's accessibility. While reviewers have offered advice on how the article could be made more accessible, none expressed concern that its level of detail was too complex. In my opinion, this subject has 'parent' articles -- like DNA repair, Genetic recombination and Meiosis -- where readers can go for a less detailed overview. The subject of this article is specific in nature, and as such I think is appropriate in its level of detail. Emw (talk) 04:47, 18 June 2010 (UTC)[reply]
After working for a few days to simplify the article, I think I may have been a bit hasty to say it was "appropriate in its level of detail." I have gone through and significantly pared back detail where it seemed unnecessary to comprehensiveness. Where I haven't been able to bring myself to cut out detail, I've tried splitting sentences up, simplifying terms, and briefly explaining jargon I feel is relevant to the point. I still have some sections to comb through, like RecF pathwayand Evolutionary origins. If you have specific concerns about the accessibility of the following sections, please let me know: Lead (still needs mention of RNA), all of 'In eukaryotes', 'In bacteria' excluding 'RecF pathway', 'Effects of dysfunction', and 'Technological applications'. Emw (talk) 06:43, 22 June 2010 (UTC)[reply]
I think you recent edits have greatly improved the article. I would not use the "see below" device because it interrupts the flow, but this is just a personal preference. Wiki linking to other sections is an option, which you have used in places, but I don't know what our current policy is on this. I understand your feelings about cutting out detail, but sometimes it has to be done. (Nothing to do with this FAC but you could consider recycling the deletions to expand related articles that are linked. That way they will not be wasted. The Spo11 article, for example, is a stub, which I tinkered with it a little yesterday). I am close to adding my support now, but would like to see more reviews from uninvolved editors. Graham Colm (talk) 11:57, 23 June 2010 (UTC)[reply]
I am going to stick my neck out on this one and add my support. The nominator has done a superb job on this difficult subject. The way the proteins described in this article—most of which are enzymes—have been named will cause some difficulties for lay readers, but I think there is little that can be done about this without compromising the article's accuracy and comprehensiveness. The nominator has gone to great lengths to improve the accessibility and I have little more to offer. I am aware of the prose review that is on-going on the articles discussion page, but I see no major obstacles in this regard in the way of promotion.Graham Colm (talk) 20:56, 25 June 2010 (UTC)[reply]
PS. As I was writing this Colin added some comments on the article's discussion page, it seems that what some enzymes do (helicases and endonucleases for example) needs a little more explanation. I think we need to say no more than an endonuclease cuts DNA in the middle, and exonuclease prunes the ends, and a helicase twists it into the double helix. I think explanatory phrases added to the sentences should suffice. Graham Colm (talk) 21:10, 25 June 2010 (UTC)[reply]
Support: For what my opinion is worth, I completely support this FAC. It has been improved since I reviewed it for GAN, which is no mean feat. It would be a proud addition to other great articles in this topic area. MasterOfHisOwnDomain (talk) 19:13, 22 June 2010 (UTC)[reply]
Comments by Ironholds
"Following the discoveries made by Gregor Mendel, it was shown that genes are often linked and do not segregate randomly. This was discovered" - discovered, twice. Can you use an alternate word?
"Double-strand breaks can be repaired through homologous recombination or non-homologous end joining (NHEJ). NHEJ is a type of recombination which, unlike homologous recombination, does not require a long homologous sequence to guide repair. Whether homologous recombination or NHEJ is used to repair double-strand breaks is largely determined by the phase of cell cycle. Homologous recombination tends to occur in the S and G2 phases of the cell cycle, when sister chromatids are more easily available. Compared to homologous chromosomes, which are similar to another chromosome but often have different alleles, sister chromatids are an ideal template for homologous recombination because they are an identical copy of a given chromosome. In contrast to homologous recombination, NHEJ is predominant in the G1 phase of the cell cycle. It occurs less frequently after the G1 phase, but maintains at least some activity throughout the cell cycle. This cell-cycle based control of homologous recombination and NHEJ varies widely between species." is entirely without inline citations
Thanks for the note. I had split the paragraph and overlooked duplicating a reference from the new second paragraph. Fixed. Emw (talk) 02:15, 25 June 2010 (UTC)[reply]
The first instance of the term is wikilinked. The second instance you're referring to is in the next sentence. Emw (talk) 02:15, 25 June 2010 (UTC)[reply]
"to cross-shaped structure known as a Holliday junction. " - a cross-shaped structure? and you've linked Holliday junction before, I'd just go with "to a cross-shaped structure known as a Holliday junction." Ironholds (talk) 02:21, 24 June 2010 (UTC)[reply]
There are several terms I link to multiple times in the article. I only link terms once per section. These terms are both technical and critical to understanding subject. While it may be overlinking, I think this violation is warranted here because the terms are especially unfamiliar to readers, and I think most readers will not carefully read the article from start to finish but rather scan through sections. What are others' thoughts? Emw (talk) 02:15, 25 June 2010 (UTC)[reply]
All the images have appropriate licences, sources and attribution. Many of these have been created by the nominator and I am impressed by their quality, usefulness and high standard. Graham Colm (talk) 13:36, 25 June 2010 (UTC)[reply]
Oppose It pains me to do this because this is clearly a very professional article and a fair chunk of it makes great effort to be accessible. The lead in particular is nearly there (see my comments on the talk). But the various pathway sections have completely lost me. I'm sure it would be useful to someone in the latter years of an undergraduate biological-science degree but as someone who hasn't even taken biology at school, I can't make head nor tail of it. But don't put me down as a "doesn't understand science" person because I enjoy New Scientist (last week's was on genetics as it happens) and am struggling through an advanced textbook on tuberous sclerosis. From what I've been able to understand I can see this is an important process and touches on several disease and how-life-works details that are interesting. I wonder if the detail of the pathway/model stuff can be moved to other (new) articles and this part rewritten in a much more basic fashion with even more diagrams and step-by-step explanations. Here's a quote from our policy page WP:NOT:
A Wikipedia article should not be presented on the assumption that the reader is well versed in the topic's field. Introductory language in the lead and initial sections of the article should be written in plain terms and concepts that can be understood by any literate reader of Wikipedia without any knowledge in the given field before advancing to more detailed explanations of the topic. While wikilinks should be provided for advanced terms and concepts in that field, articles should be written on the assumption that the reader will not or cannot follow these links, instead attempting to infer their meaning from the text.
As I said, the lead and some other sections are pretty close to meeting this policy requirement. I appreciate that a 12-year-old isn't even going to read this article. Think more "New Scientist reader" and you won't go far wrong. Colin°Talk21:02, 25 June 2010 (UTC)[reply]
I hope the nominator will not mind my responding. Would a glossary section like the one here be helpful? I agree that more diagrams would also be helpful and that spin-off articles could be expanded and linked. (I made this point above, WRT to Spo11). I am not entirely convinced by the "New Scientist argument"—I think we can, and often do better. I have read some very poor articles in New Scientist; they often over simplify and frequently make mistakes IMHO. Graham Colm (talk) 22:42, 25 June 2010 (UTC)[reply]
You know, I knew I'd get a "New Scientist oversimplifies and is full of errors" response :-). I'm more concerned with the target-audience aspect than the material it contains. Some people on WP think we should aim at 12 year olds, but that is unrealistic for this article. Others think that having articles only an undergraduate could follow is acceptable. The other aspect of New Scientist is that its articles must be capable of being read without having a biology reference textbook open at your side. I'm sorry if my talk page comments make anyone despair that someone so ignorant that they need basic biological terms like somatic, eukaroytes or meiosis/mitosis defined for them could possibly hope to understand the pathways and mechanisms of homologous recombination.
The descriptions of the various mechanisms involved are very complex. I also got the impression (though can't find the words at present) that some of this is conjecture. To what degree are these pathways known for sure? A glossary may well help some of the article particularly if a difficult word is used several times so the reader might have forgotten the definition given earlier. My problem with the mechanism bit is I can't really visualise it and because it is so alien and complex, I can't hold the description in my head. Do any of the textbooks you have treat this in a simpler way? Colin°Talk09:09, 26 June 2010 (UTC)[reply]
I run into the complexity vs. comprehensiveness problem frequently, and often have problems understanding my own sources when they dive into fine details on anatomical structure, particularly with skulls and teeth... and I have a degree in evolutionary biology! Although I don't have time to dive into a thorough review of this article, I feel that if the article meets all other criteria and is understandable (sufficiently linked and explained) by someone who is beginning studies in the parent field, then the article should pass. Any area of study has its own terminology and assumes varying degrees of experience to understand. You can't reasonably explain a comparative anatomy study to someone who's never studied biology and doesn't understand evolution... not without going significantly off-topic. You can't explain calculus to (most) students just learning the ins-and-outs of algebra. In my opinion, there should be no "standard" that applies universally to all Wikipedia articles. Technical articles should be sufficiently explained and linked, and certainly should be written not necessarily for the expert but for someone who has an appropriate background and an introductory interest in the topic. An article on broader or generally popular topics, such as Mathematics, Evolution, Rodent, or Shania Twain should be readable by a very broad audience. Articles about Euclidean algorithm, Homologous recombination, Oryzomys, or maybe Franz Kafka could be written at higher reading levels, depending upon their exact content. Even within the articles, if the material is simple, write it simply. It's the lead that needs to be written the simplest. (In the case of this article, only the 2nd paragraph in the lead seems to be a little too detailed or complex.) If a topic is complex, write as simply as you can without making errors, misleading the reader, or losing important detail. In other words, as long as this article meets all other criteria, is comprehensive, and is written for the broadest audience possible given the topic level, then I would support passing the article. Just my $0.02... – VisionHolder « talk »16:54, 26 June 2010 (UTC)[reply]
The middle half of this article is at a level more suited to an undergraduate textbook than an encyclopaedia for the general reader. If we want to start aiming our articles at 1st and 2nd year biology undergraduates then that's a discussion to have over at the policy pages. People look to featured articles as an example to follow. There is a danger that we will encourage our biology articles to become impenetrable to the general reader. Would this content be accepted by Encyclopaedia Britannica? BTW: I have no problem with other editors challenging my oppose. I do congratulate the editor(s) on the remarkable accessibility of much of it. Colin°Talk20:15, 26 June 2010 (UTC)[reply]
I've gauged the complexity of this article using two assumptions. The first is along the lines of what VisionHolder mentioned. That is, top-level articles in a scientific or technical subject area should strive to be general and very accessible; lower-level articles are inherently more detail-oriented and thus less accessible. While it is an important mechanism in biology, homologous recombination is not a top-level subject in biology. As I've noted in comments to GrahamColm, I consider this article to have higher-level 'parent' articles: DNA, DNA repair, Genetic recombination, Meiosis, etc. The second assumption I've made is that the accessibility of this article should approximate that of similarly-scoped featured articles in molecular biology, for example RNAi and Exosome complex. In that respect, and as I have mentioned previously, I think this article is far more accommodating to lay readers. Emw (talk) 22:48, 26 June 2010 (UTC)[reply]
With regard to a glossary: would entries for the following terms help? "Mitosis", "Meiosis", "Double-strand break", "Resection", "Strand invasion", "Holliday junction", "Branch migration", "Resolution". Let me know which terms should be added or removed. And for diagrams, which would be the most helpful? I can make one or possibly two quality diagrams in the near term Emw (talk) 22:48, 26 June 2010 (UTC)[reply]
I may not be able to find the time at present to give you the reply you deserve and to study the recent changes. Speaking abstractly, this two-tier Wikipedia with some accessible articles and other impenetrable articles (for experts only) doesn't have any basis in policy. I can see a hyperlinked information-base working that way, but it isn't how Wikipedia was set up. It is a general purpose encyclopaedia for the general reader. Just like New Scientist and Brittanica must reject or send-back-for-revision some brilliant articles because they fail their editorial policy on readership, so should we care that our featured articles represent the best of what Wikipedia can produce for its target audience. I have sympathy with the great difficulty this poses for our advanced topics (and think perhaps the wider-scope genetic recombination would be an easier choice for FA) and ultimately it may greatly restrict what we can say. It might be that it is just not possible to explain to a general reader how Homologous recombination works within the space of a decent sized article. Perhaps all we can give them is the flavour. On my user page is a quote: "It is our job to interest [our readers] in everything. It requires the highest degree of skill and ingenuity." It does indeed. Colin°Talk14:54, 27 June 2010 (UTC)[reply]
Feel free to bring this topic up at WP:VPP. I'll gladly join the discussion. (Just notify my on my talk page if you do.) But let me be clear about two things. First, I am not suggesting a two-tier Wiki, just a graduated Wiki (simple text for simple topics and gradually more complicated text for more complicated topics—with all topics requiring a generally simply lead). Second, I don't feel articles should be written for experts, but maybe for students coming into the field. I won't go into reasons or debate it further because this isn't the place. I only wanted to voice my opinion that this article shouldn't be held up on these grounds. Just my $0.02. – VisionHolder « talk »15:46, 27 June 2010 (UTC)[reply]
Colin, for perspective, consider that Britannica doesn't even seem to have an article on homologous recombination. The closest thing I see is here -- a 176-word stub confusing genetic recombination and homologous recombination as it occurs in meiosis. I note this example because I think it's roughly what Wikipedia's coverage of many non-top-level science topics would be like if your editing philosophy were followed. In my opinion, an accessibility standard along the lines you seem to propose would require a massive recalibration or demotion of many non-top level molecular biology FAs, including Enzyme kinetics, Enzyme inhibitor, Cyclol, Antioxidant, RNAi, and Exosome complex.
I have responded to the concerns you listed at Talk:Homologous_recombination#Comments_by_Colin. While it seems we have some disagreements about the appropriate level of detail for this article (and non-top level science articles in general), the specific concerns you listed on the article's Talk page have been quite helpful. Emw (talk) 16:22, 27 June 2010 (UTC)[reply]
This is a tricky problem. I'm afraid I don't have any more time at present. There's a policy issue here that should perhaps be discussed in a wider forum. I've said my piece and if the consensus is against me this this "oppose" will be ignored, and that's fine. Colin°Talk18:47, 27 June 2010 (UTC)[reply]
You're right, it is a tricky one. If it is a policy issue, perhaps it is unfair to make this FAC a test case. I agree that sections of the article can be mind-boggling to some readers, but the article is of a similar standard to quality text books on the subject (those listed under my strikes above for example). Text books usually lack the full complexity of review papers and monographs and this article is similar in this respect. I think much progress can still be made in reducing the jargon—particularly with regard to the names of the enzymes involved. But I think we have to consider readers and teachers who cannot afford textbooks—would we be doing them a disservice by offering less than a standard textbook on the subject? Bye the way, there is nothing conjectural here, it's a well-sourced description of the currently accepted mechanisms. No doubt these will change in time, but so will this article. Graham Colm (talk) 19:30, 27 June 2010 (UTC)[reply]
On reflection, I think I am forgetting the all important Featured Article Criteria; my comments immediately above, especially those about the availability of good textbooks, is possibly off topic. I am concerned that the prose is not engaging. I am not withdrawing my support, but could the closing delegate take my reservations into consideration? Graham Colm (talk) 23:16, 28 June 2010 (UTC)[reply]
Could you elaborate a little bit on your concern that prose is not engaging? Is it distinct from a concern that the article is "going into unnecessary detail" (WP:FACR 4)? If so, could you offer some actionable suggestions to make the prose engaging? If not, could you comment on how far the work done in the past week (summarized below) goes in addressing your concern about unnecessary detail and inaccessible jargon? Emw (talk) 15:51, 4 July 2010 (UTC)[reply]
Remaining issues: I'd like to get an idea of what remains to be done. In the long discussion above I see something resembling a request for more diagrams and a glossary. For diagrams, I can make one or possible two in the near term, but I'd like to know what I should be making them on. For a glossary, I'd like to get others' opinion on whether one for the following terms makes sense: "Mitosis", "Meiosis", "Double-strand break", "Resection", "Strand invasion", "Holliday junction", "Branch migration", "Resolution". What terms should be added, which should be removed? Also, it seems that reviewers would like enzyme jargon to be reduced -- but where, and to what degree? Other notes on specific and actionable work to be done would be appreciated. Emw (talk) 12:02, 28 June 2010 (UTC)[reply]
I think we have to resolve problems like this, "working in conjunction with Slx4 and Saw1". We can't rely on just wikilinking, we have to add something like, "enzymes called....that". This seemingly, throwaway use of enzyme nomenclature is the highest obstacle to promotion IMHO. Graham Colm (talk) 23:16, 28 June 2010 (UTC)[reply]
I've fixed the drive-by mention of Slx4 and Saw1. That section, SSA pathway, has been reworked to have a clearer narrative that should make it easier to follow. I have also added more relevant information on the role of specific proteins in the larger process, which hopefully adds context and not simply detail.
I have also drastically reduced the size and level of detail in the RecF pathway section. The section now mentions only one specific protein, which was mentioned previously and is probably the most important enzyme in homologous recombination. (I've moved the more detailed material into a new child article, RecF pathway.) Emw (talk) 06:32, 29 June 2010 (UTC)[reply]
I've just now gone through the article and ensured that the first reference to every protein explicitly notes that the referent is indeed a protein (e.g 'the RuvB protein' instead of simply 'RuvB'). I have also indicated the function of every protein mentioned in the article. With this, I consider the concern about "throwaway use of enzyme nomenclature" to have been addressed. In addition, I've gone through another significant sweep of the article in my effort to exhaustively define every piece of jargon at (or near) its first occurrence -- or to add context which indicates the jargon's meaning. Emw (talk) 07:31, 3 July 2010 (UTC)[reply]
The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.
