Talk:DNA repair protein XRCC4

Some ideas for improving the Wikipedia page for XRCC4

Regarding ways to improve the Wikipedia page for XRCC4, there is much work to be done since the current Wikipedia article for XRCC4 is still only a stub article. It contains a very simple lead section and only a few other sections. Moreover, each section only covers the most basic scientific background with much of the most important content missing. The current stub has two images of the protein but an image of the mechanism for non-homologous end joining with other proteins involved should also be included. Furthermore, the information from section to section is not cohesive and the article was most likely written as a mere starting off point.

Based on Unit 5's "Style Guide and for Gene and Protein Articles", it should include more background information in the lead section (instead of just one sentence) and establish why the topic is notable. The lead should cover a sufficient amount of information on XRCC4 so the reader can obtain a relatively thorough understanding on the topic, while providing enough detail to encourage the reader to delve deeper by reading specific sections in the remainder of the article. For example, the lead should specify the importance of having the NHEJ mechanism to rescue DSB that are generated prior to DNA replication, the cascading effect of proteins Ku70/80, DNA-PKcs and Artemis, and how XRCC4 acts in concert with Cer-XLF and Ligase IV to form a complex in order to repair the DSB, and explain the detrimental effects of having mutations in XRCC4 and these proteins touching on the diseases that result. It should also include a Gene and Protein section with fundamental information such as the chromosomal location of the gene, exons, protein splice variants and structure and domains (including images). For the Function section, it would be important to explain what DNA damage is, the different types, repair mechanisms, and what would happen if these damages are not repaired, especially for DSB that require NHEJ for repair (why pre-replicative DSB are the most damaging). This will help the reader put XRCC4 and NHEJ into a clearer context. Very specific details of the mechanism of the protein which highlight the structure of the binding site of XRCC4 and how it complexes with Cer-XLF and Lig IV, as well as binding or catalytic sites of the other proteins, and the mechanism of NHEJ. The regulation of XRCC4's gene expression. its location in the nucleus of the cell, and how its interaction in the cell can be visualized. The pathology section can cover known mutations and diseases they cause, the clinical significance of understanding potential drug targets, and ways to reduce DSB's. Experimental techniques section can cover current methods or technologies being used for studying protein homology and to discover or validate new mutations in the Xrcc4 gene and its regulatory sequences and how these findings can help to create more effective companion diagnostics and therapeutics. To make it really complete, a history section on who discovered the protein. Furthermore, there are many recent publications regarding XRCC4 that have not been taken into account or otherwise cited. Taking the above parameters into consideration combining with citing excellent peer-reviewed references in an accurate and original way should bring this article into an excellent article. Jgould1400 (talk) 04:16, 14 March 2013 (UTC) Cdunca12 22:12, 17 March 2013 (UTC)

Comments from Binhtruong (Responses in Italics)

This article seems like its heading in the right direction and has improved tremendously. With that being said, here are some feedbacks you might consider for your next contribution.

1) Correction in lead section: PRKDC is a gene and not a kinase subunit. I believe article is referring to the enzyme subunit DNA-PKcs, which is encoded by the PRKDC gene referenced in first citation.

The information was wrong for PRKDC. An editor had added paragraphs two and three in the lead section and they need to be re-edited. The wording was also awkward. I have already changed this.

The information was correct for PRKDC and was taken from:

"The core NHEJ machinery includes XRCC4, DNA ligase IV (LIG4; 601837), and the DNA-dependent protein kinase complex, which consists of the DNA end-binding Ku70 (G22P1; 152690)/Ku80 (XRCC5; 194364) heterodimer and the catalytic subunit PRKDC (600899)."

— Mari et al., 2006, OMIM

While a little sloppy, gene and protein names are sometimes interchanged as in the OMIM entry linked above. It would have been more proper for the displayed link to be DNA-PKcs instead of PRKDC but both link to the same article whose subject matter is about the enzyme and the gene encoding that enzyme. Boghog (talk) 20:23, 29 April 2013 (UTC)

2) Illustrations of graphs are difficult to follow since there is no text reference. Perhaps remove the graphs completely or provide a thorough explanation for its purpose.

These graphs were a part of the original article and have been omitted.

3) There is too much emphasis on causes for double stranded breaks. I believe briefly mentioning and describing it would suffice. There is already a wiki page reference for DSBs so no need to elaborate too much on it.

Although this section is relatively long, the content is very important in establishing notability and helps the reader understand how DSB can be lethal without NHEJ. I may shorten it just a bit.

4) Role in DSB repair section seems to already describe the mechanism behind XRCC4, thus perhaps merging this section with the mechanism section.

Yes - I have removed the second paragraph and removed the mechanism section and just changed the section name for Role in DSB repair to “mechanism”.

5) The Interaction section needs more information or seems repetitive since XRCC4 has already been mentioned to interact with ligase IV in previous sections.

Once I add new information in the structure section which will cover binding sites and interactions with other proteins, we may remove this section.

6) Anti-XRCC4 antibodies are thoroughly described but have no relevant information on its purpose. Perhaps article can describe how these antibodies are utilized.

This has now been done. Jgould1400 (talk) 03:39, 25 April 2013 (UTC)

7) Additional content is needed on the structure of XRCC4 and post-translational modification.

I will be adding this in the next couple of days.

8) Subsections under Pathology category seems out of place. Perhaps create another section for XRCC4s role in therapeutics and its contribution to scientific discovery. In addition, more content is needed for some of the pathologies described. Additional content and references have been added in several places.Jgould1400 (talk) 04:15, 26 April 2013 (UTC) Thank you for all of your input and taking the time to review our article!

Good luck! Binhtruong (talk) 00:03, 9 April 2013 (UTC) Cdunca12 05:01, 24 April 2013 (UTC)

Comments From JMUDukes88 (Responses in Italics)

1. I appreciate the additions you added to this article. Plus, you have a ton of relevant sources complementing your statements!
2. The second sentence in the lead section is a bit confusing. "This gene contains 8 exons, and alternative transcription initiation and alternative splicing generates several transcript variants". Perhaps, you could use this? "This gene contains 8 exons, an alternative transcription initiation [compared to...], and [internal alternative splicing mechanisms to generate several transcript variants]."

I agree. An editor came in and added this paragraph. I have already removed both the second and third paragraphs and added three new paragraphs which summarizes the article in concise way and addes better notability.

As several other reviewers have mentioned elsewhere, the subject of this article is the XRCC4 gene and protein and not the NHEJ pathway. The lead should give a brief introduction as to why this protein is notable (because it participates in the NHEJ pathway), but nevertheless should focus on XRCC4. The lead should also summarize the main points of the article. The material that I had added to the lead was an attempt to provide some basic information about the main subject of this article. While the phrasing of that material could certainly be improved, I think some of this information (starting with the first sentence, see below) should be re-added. Boghog (talk) 07:13, 1 May 2013 (UTC)

1. The lead section properly defines the topic, sets the context of the article, but I think you can add to how XRCC4 is notable. You mentioned it is involved in NHEJ, but I think the notability comes from what NHEJ is important for (in a sentence).

The last sentence in the second paragraph mentions the importance of NHEJ in preventing losses of long chromosomal regions.

1. The lead section probably could use references pertaining to the last two sentences in order to strengthen the statements starting with "Certain polymorphisms..."

I can add one more sentence to mention a couple of specific cancer-related diseases that Jim has elaborated on further into the article.

1. Have either of you considered moving the "Structure" section to follow the lead? I think this area would fit perfectly to go with the great thumbnail of the protein. I also have seen other pages operate in this manner. For example, DNA. The section "Properties" seems analogous to your "Structure" section.

I have moved the structure section after the background on DSB. I think it makes more sense to have this background first before going into the protein structure and mechanism more in-depth.

1. Merging “Interactions” with “Structure” may be able to extend the "Structure" section. This would make it stronger in following the lead.

The interactions section may be extraneous as the information is repeating parts of the Mechanism section.

1. Would either of you consider looking into adding content on how the specific structure contributes to function? For example, “The C-terminal domain consists of a single extended alpha helix that is wound into a four-helix bundle in the tetramer. This interacts with… of the DNA…”

Yes – that is what I have in mind.

1. What about moving “Mechanism” to become a subsection of the section “Role in DSB repair”.

The mechanism of NHEJ is very important and XRCC4 plays a major role, so it should have its own section.

1. Under the heading “Pathology”, it seems a short summary is needed. For example, “XRCC4 has been associated with several…” I don’t think the heading can stand alone before introducing the subsections.

I think Jim may have just added this summary. It looks good. Yes, this has now been done. Thanks for your comments. Jgould1400 (talk) 03:43, 25 April 2013 (UTC)

1. Would you consider removing the image showing the "Gene expression pattern of the XRCC4 gene"? I can't see it's relevance to what is stated in the article besides it being the XRCC4 gene.

"Do you mean the RNA expression pattern? This is the expression pattern in different tissues. I think it gives an idea of the types of DNA damage or in this case, DSB, that occur in the cells of different tissues and that NHEJ is being used to repair this damage. It needs an explanation. If you click on the image to enlarge it, it will be more clear."

Yes, I was referring to that image and could understand what it was entailing. I just thought it was a bit of a headache haha, but it definitely shouldn't stand alone. I didn't see that you had mentioned the XRCC4 gene expression pattern in the article or made reference to the variable expression in different tissues when I made this comment. Maybe adding a bit of that info would suffice? Jmudukes88 (talk) 01:16, 28 April 2013 (UTC)

''I will consider where in the article I would include this. I may include a simple explanation in a new subsection.

1. The addition of the image "Non-homologous end-joining" is great!

Thanks

1. Under the "Double strand breaks" section, I would consider creating a list (numbered by using the "#" function) of the examples of DNA damage. This is just for aesthetics in order to clean up the paragraph. This could encourage you/the Wiki community to possibly add more examples of double strand breakage! Also, this area is pretty high in different links and some jargon. It would help break these up a bit.

The links are relevant to the subject matter and will help the reader understand the overall information better. Can you specifically mention which words are considered jargon? I tried to describe the information in a very clear but descriptive manner as mechanisms are difficult to understand. I wanted to add different types of DNA damage, but was concerned about the length of this section.

I was actually referring to all of the text that is now under the "Sources of DNA Damage" subsection. I like how it stands now because of the organization within the larger section, plus you have linked those words that seemed moderate-to-heavy in jargon (ROS, singlet oxygen, etc.). The linking caused the text to standout and makes it clearer to read upon first glance, plus easier to find info on the material for the casual user of Wiki. Nice work! Jmudukes88 (talk) 01:16, 28 April 2013 (UTC)

Thanks! I think it does flow much nicer now and the links provide clear resources to obtain more background info on it. Cdunca12 05:18, 6 May 2013 (UTC)

1. There is a sentence under the DSB section that is without reference (and I believe you had meant to have one). "However, if the DSB is generated prior to synthesis of the sister chromosome, then the template sequence that is required will be absent (6)."

Thanks – I’ve corrected this.

1. I noticed "Role in DSB Repair" could be more aptly named "Role in DSB Repair of NHEJ" because it is in accord with the first sentence of the lead section: "... XRCC4, is one of several core proteins involved in repair of DNA double strand breaks in eukaryotes during non-homologous end joining (NHEJ)”.

I have re-organized this section and just made one “Mechanism” section, and removed the two extraneous paragraphs from the original article. They repeated what I included in this mechanism section.

1. Would you also consider outlining or making a numbered list for the steps in "Role in DSB Repair"? The heavy jargon (from protein names) seems very intimidating. I feel creating a step-wise list of XRCC4's role in repair would potentially clean this up.

Let me consider the step-wise list. I actually thought the steps require more details about how the binding sites interact, very specifically. I didn’t really want to take away the consistency of the paragraph format, but I understand your point.

1. "Pathology" I a great section in it's content. I'd consider pairing each study area with it's diagnostic area. I will show an example here (without re-structuring the Talk Page) because it is tough, for me, to communicate effectively.

==Pathology==

===Cancer susceptibility===

====Potential use as a cancer biomarker====

We will consider this. Jim, what do you think? I've left the structure as is; I think it flows nicely.Jgould1400 (talk) 04:09, 26 April 2013 (UTC)

Overall, I think the all the sections follow the guidelines such as the leads section (there are improvements mentioned in my comments/list). The writing is clear, but harder to understand only because of the nature of XRCC4, rather than the writing. I made all of my comments on how to clear up some of that technical jargon and I think they would help by making the activity in a stepwise fashion. The sections work in harmony with the proceeding content, but as you can see in the list above, I believe there could be great re-structuring/organizing of those sections. Luckily, we have some time to do this whether you choose to or not! The references that I checked hold accurate citations without material that is directly copied.

In regards to numbers 6 of my comments, I wanted to give sight to an area where you can find more substance to add in your section, "Structure". Your reference, Crystal structure of the Xrcc4 DNA repair protein and implications for end joining, is actually ripe w/ more content for the Wiki. Just looking through the references you can find other articles to find content on structure (related to function) as well. For example, the study mentions that the C-terminal stalk of XRCC4 interacts with DNA ligase IV suggesting a possible method for ligase coupling to DNA. Jmudukes88 (talk) 02:22, 12 April 2013 (UTC)

Yes- this is exactly what I have in mind in terms of structure. I will be adding new information in this section in the next couple of days. Thank you very much for taking the time to review our article. Cdunca12 05:21, 24 April 2013 (UTC)

Review from Klortho (Responses in Italics)

First, I read through the reviews of your classmates above, and I think they are great, and have a lot of very useful suggestions. I would add a few of my own comments/suggestions (I did this quickly, so there might be some overlap with the suggestions from your classmates):

• The first sentence in the lead is a little too hard for a layman to understand. Could you simplify the language a bit? For example, you wrote, "... during NHEJ", which, when I first read it, made it sound as if the DNA breaks occur during some process called NHEJ. It is not clear that NHEJ is part of the process of the repair.

I will try to re-word the first sentence and maybe break it up into two sentences.

• This is a generally suggestions for the lead: could you try to simplify the language?
• In the lead, you use the word "polymorphism" to refer to a gene, and link to the polymorphism article. But in that article, they say, "This usage is not discussed in this article." Could you use a different term?

I have removed the second and third paragraphs in the lead as another editor came in and inserted them. I have added three new paragraphs which concisely describes DNA damage, DSB, the basic mechanism of NHEJ, and mutations in XRCC4.

Because someone else added this material is not, in itself, a valid reason for its removal. Of course, if the material is not relevant it should be removed or if it is poorly written, it should be edited. To reiterate, the material was added in an attempt to provide information specific to XRCC4 in the lead. Boghog (talk) 19:05, 1 May 2013 (UTC)

• In the opening of "Double strand breaks", for example, when you write, "a variety of both exogenous and endogenous genotoxic sources". Couldn't you simplify the language, and just write "a variety of causes"?

Exogenous means environmental or external, and endogenous means internally and naturally derived from cellular metabolism.

• Link "γ radiation"
• In the sentence with this phrase, " targeting the cell for apoptosis": link "apoptosis". Also, does the incomplete copy of that chromosome really target the cell? In other words, I think this sentence is a little bit confusing.

I will elaborate a bit on this. If there are key proteins that are not translated and aren't available for certain functions as a result of the loss of that specific region of the chromosome, then the cell will be targeted for apoptosis.

• The old revision (before this class started) had a protein family infobox. Why was that removed?

• Why did you remove the PBB_Controls template? (See this edit)

No one removed this. I'm not sure what this is.

• Do something with the "Post-translational modifications" section, which is currently empty. Either add content, or remove the header.

I put this section in as a place holder. I have not had the opportunity to do the research yet but will by unit 14 for my last contribution.

Thank you for all your input and help! Cdunca12 05:44, 24 April 2013 (UTC)

Hi Klortho. Thank you for taking the time to discuss this page by phone; and, separately, thank you for your assistance in restoring the portions that you wanted restored. Revisions are underway that will address additional points that you have raised. (See especially the recent revisions by my teammate, Cdunca). Please let us know if you have any further comments or questions.Jgould1400 (talk) 02:51, 24 April 2013 (UTC)

..

Klortho (talk) 13:58, 21 April 2013 (UTC)

It seems that the infobox was removed by User:Boghog, please disregard those comments. I'll ask him about that. Klortho (talk) 19:12, 21 April 2013 (UTC)

Actually, another correction. The infobox I was talking about was the one that's now under the "Structure" section, and it is still in the article. I was going quickly, and hadn't noticed that it was moved instead of deleted. Sorry for the confusion! Klortho (talk) 19:32, 21 April 2013 (UTC)

Sorry. I didn't realize that this article was the subject of a course assignment. I will hold off on further edits until the course is done. Please note that the PBB controls and templates are no longer used by User:ProteinBoxBot to maintain Gene Wiki articles and hence are deprecated (see for example this discussion). I therefore removed the controls to reduce the clutter. The original {{pfam}} template (and graphic) was for the N-terminal domain of the XRCC1 protein. This domain is not contained in the XRCC4 protein. I therefore made the appropriate correction in this edit. I also moved the pfam box to the structure section which I believe is an appropriate section to place this box. Boghog (talk) 19:53, 21 April 2013 (UTC)

Thanks, and thanks again for the explanation about the infoboxes. Klortho (talk) 16:43, 22 April 2013 (UTC)

External review

Overall, there are tremendous improvements in the article. I do have a couple of suggestions however.

The subject of this article is the XRCC4 gene/protein that is involved in the NHEJ pathway of DBS repair and not the NHEJ pathway per se. This is a subtle but important point. A brief introduction to NHEJ pathway and DBS repair is appropriate, but shouldn't overwhelm information specific to the XRCC4 protein. One should refer to the background articles, but not attempt to fully duplicate the information already contained in these other articles.

Per WP:LEAD, the beginning of the article should define the scope of the article (XRCC4 gene/protein), provide a very brief introduction to the topic and why it is important and also summarize the main points of the article. The lead should also be written in way that it can be understood by a wide audience. The current lead lacks some fundamental information about XRCC4, for example species distribution:

• In humans the X-ray repair cross-complementing protein 4 is encoded by the XRCC4 gene. In addition to humans, the XRCC4 protein is also expressed in many other metazoans, fungi and in plants. (ref: "DNA repair protein XRCC4 (IPR010585)". InterPro. EMBL-EBI. which in turn cites PMID 11029705)

A dead simple explanation why it is important:

• Certain mutations in the XRCC4 gene are associated with an increased risk of cancer. (ref: PMID 23321468)

A simple description of the composition of the NHEJ complex with wiki links to the other component of the complex:

• The NHEJ enzymatic complex includes XRCC4 (this protein), DNA ligase IV (LIG4), a DNA end-binding Ku70 / Ku80 heterodimer and a kinase subunit DNA-PKcs. (ref: PMID 17124166)

The details of the mechanism are way too technical to be included in the lead.

Also in response to the above comment: "The information was wrong for PRKDC." The information is correct since the PRKDC article is about both the gene and the kinase encoded by the gene, although it was not as clear as it could be and can easily be fixed with a piped link (i.e., [[PRKDC | DNA-PKcs]]). Boghog (talk) 20:54, 24 April 2013 (UTC)

Progress Report for Units 11-12

A very substantial amount of new material was added since our last progress report, including the new section on "History and Identification of the XRCC4 Gene", the new section on "Anti-XRCC4 Antibodies", and the new subsection on "Endometriosis Susceptibility" that was added to the Pathology section; and in addition, information and content was consolidated in several locations and many references were added. We have also considered the various comments we received and have made revisions and additions where appropriate. Jgould1400 (talk) 03:57, 26 April 2013 (UTC)

I have made what I thought were a few constructive suggestions above that were not taken into account. Hence I hope you don't mind that I have now included them in the article with these edits. Keep in mind that it is important to include appropriate links to Wikipedia articles. This article does not exist in isolation. Also please keep in mind that the lead to an article is not just an introduction. It also should summarize the important points in the article. Finally it is important not just to interact with classmates, instructors, and ambassadors when editing a Wikipedia article as part of a class assignment. It is also important to interact with other editors. Boghog (talk) 20:46, 29 April 2013 (UTC)

Thank you for taking the time to review and edit our article. The article is not yet completed and work to be added or editing is still an ongoing process until next week (unit 14), which is the last week of class and the last major contribution to the project will be made. I just added the "Structure" subsection under "Properties" this morning and was going to add the links tonight. I agree that the lead section is also a summary of the whole article and wanted to add one more sentence at the end in regards to DNA damage leading to different types of cancers. Thank you. Cdunca12 00:51, 30 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Article title and first sentence (Responses in bold and Italics)

Per WP:LEAD, "The lead should define the topic and summarize the body of the article with appropriate weight.". Furthermore the lead should ideally define the topic (i.e., scope) of the article in the first sentence in a drop dead simple manner that can be understood by a wide audience.

As discussed here and here, we have tried to make clear that these Gene Wiki articles are not only about the human gene/protein, but also orthologs that exist in other species. The wording that was reached through consensus is perhaps a little awkward, but it is both accurate and concise:

• <recommended UniProt name> is a protein that in humans is encoded by the <approved HUGO gene symbol> gene.

The "that" in the above sentence is non-limiting implying that the protein (and gene) exists in other species besides human.

Hence I suggest that this article be renamed after the protein (DNA repair protein XRCC4) and the first sentence be changed to:

• DNA repair protein XRCC4 also known as X-ray repair cross-complementing protein 4 is a protein that in humans is encoded by the XRCC4 gene.

I will clarify to see which protein name is the correct one in humans. I may make this modification.

The name I suggested above is taken from Q13426 which specifically refers to the human variant [and is identical to mouse (Q924T3), slime mold (Q54YJ7) and most other species except for the capitalization of XRCC4 which follows the standard convention, human – all caps, other mammals – only first letter capitalized, non-mammals – lower case], Boghog (talk) 06:59, 6 May 2013 (UTC)

In the current version of the article, the XRCC4 gene is first mentioned in the last paragraph of the lead. I believe it should be included in the first sentence of the first paragraph. Thoughts? Boghog (talk) 21:25, 29 April 2013 (UTC)

I think the lead suffices in the summarization of the article. It has a basic background of DNA damage and DSBs, protein mechanism, and mutations in XRCC4. I may add one more sentence about different mutations leading to cancers in the last sentence. Cdunca12 05:51, 6 May 2013 (UTC)

The current lead contains too much introduction to the NHEJ pathway and not enough summary of information specific to XRCC4. As the article is expanded, the lead will require periodic editing so that it reflects the contents of the article. Boghog (talk) 06:59, 6 May 2013 (UTC)

What specific sections do you want to see better represented in the lead? I would say Pathology and maybe a little bit more about post-translational modifications. Thoughts? Keilana|^{Parlez ici} 21:30, 9 May 2013 (UTC)

I agree pathology should more prominently mentioned in the lead, particularity its use as a biomarker. I also note parenthetically that the subsection on potential role in therapeutics needs some work. XRCC4 SNPs mentioned in the first part of this section are effectively biomarkers. The rest of this section is a bit fuzzy. Drugs that specifically inhibit XRCC4 theoretically might be useful in cancer treatment but we would need a reliable source to document this proposed use. Boghog (talk) 22:08, 9 May 2013 (UTC)

A bunch of revisions were just made by me in an effort to address BogHog's comments regarding the pathology section. Jgould1400 (talk) 07:56, 16 May 2013 (UTC)

Comments from Aluquette (Responses in Bold and Italics)

Overall I am really impressed with your article! It looks like you’ve significantly improved it. I know we only have a week of class left so I’ll try to be brief with my suggestions.

I think the lead could use a little more info on the XRCC4 protein itself. After reading the lead it feels like the focus is on DNA repair and not XRCC4.

The lead isn't supposed to contain more than four paragraphs. The original lead I created was too long and ended being my main section. I will consider adding one or two sentences for XRCC4 properties.

Adding one or two additional sentences about the XRCC4 protein to the lead is not going to cut it. The four paragraphs of the lead should focus on the XRCC4 gene/protein and not the NHEJ pathway. The longest paragraph in the current lead (paragraph #2) doesn't even mention XRCC4. Furthermore the section in this article on double strand breaks really should be merged into the double strand breaks section of the DNA repair article. Boghog (talk) 19:40, 7 May 2013 (UTC)

I see some of the other reviewers have already suggested reducing the amount of info on DSB and the repair pathways… I know you spent a lot of time writing so if you consider reducing these areas perhaps you could move that content to other articles on Wikipedia (like DNA repair). Just a thought.

I know it seems long, but this section really helps the reader understand why NHEJ is important before they can understand XRCC4 and why this protein is critical in NHEJ. I will be adding more information in the Properties section of the protein, so it will be more complete.

The structure section is very detailed but I think it would be really helpful if there was a visual like the one at the top to look at while reading it. Without a visual it’s hard to picture what you’re talking about. Maybe you could move the structure section to right after the lead so it’s closer to the picture or find another picture to put with the structure section.

Good point. I am working on finding a more detailed image right now. I don't think I will move the Structure section as it falls under Properties.

This sentence was mentioned in previous reviews (and sounds like it wasn’t written by you?) “The human XRCC4 gene contains 8 exons, and alternative transcription initiation and alternative splicing generates several transcript variants.” I think it would read easier if it were two separate sentences – “The human XRCC4 gene contains 8 exons. Alternative transcription initiation and alternative splicing generates several transcript variants.” And if you have time, maybe say a little bit about the variants (do they serve different purposes, etc).

This sentence was originally a part of the lead before we started editing. I removed it and it was added back in again by editors. I will add more info in the Gene and Protein section.

A more detailed explanation was already provided below. Also why am I being referred to in the third person plural? ;-) Boghog (talk) 20:12, 7 May 2013 (UTC)

Hope my suggestions help! Aluquette (talk) 00:48, 1 May 2013 (UTC)

Yes - they certainly helped. Thank you for taking the time to review our article. Cdunca12 06:03, 6 May 2013 (UTC)

Just a clarification and some history about the "human XRCC4 gene contains 8 exons ..." sentence. This sentence was first added to the article by me in February 2008 to provide seed material that could later be expanded by other editors. This material was copied from Entrez. Because this material is in the public domain (see {{NLM content}}), including it in a Wikipedia article is considered fair use as long as proper attribution is included (citation). I have restored this sentence twice after it has been deleted, first to the lead, and then to the gene section because it describes basic facts about the XRCC4 gene that should be mentioned somewhere in this article. By all means, please edit the sentence to improve its clarity and expand on it. That was and still is the intention of including this seed material. Boghog (talk) 07:41, 1 May 2013 (UTC)

Thanks for the clarification, Boghog. I went ahead and made it two sentences but I'll leave it up to my classmates if they'd like to expand that section. Aluquette (talk) 23:30, 1 May 2013 (UTC)

And thanks for your edit, Aluquette. That looks great. Boghog (talk) 14:33, 4 May 2013 (UTC)

Thanks for editing this portion. I will add more information to the Gene and Protein subsection and will combine this as well. Cdunca12 06:03, 6 May 2013 (UTC)

Comments from Er1cah0p3

This article really seems to have been tremendously improved.I think the citations are appropriate and correct. The content has a very nice flow and all sections have ample information. All of the improvements suggested, and followed, by other editors have really added to the overall quality of the article.

I am in agreement with Aluquette regarding the addition of a visual aid to the structure section if one can be located but I know this can be difficult. I think that the DSB information in the introduction is fairly extensive but I do not know that it distracts from the article all that much. I also believe that it may be necessary for explaining the importance of XRCC4. The only other suggestion that I would offer would be to move the history and identification section to the top of the article underneath of the introduction. This may help pull attention back to XRCC4 and then get back into the DSB information.

Great work so far!!Er1cah0p3 (talk) 00:20, 2 May 2013 (UTC)

Thanks very much for your kind words. Regarding the placement of the History section, my thought was to place it near the end so as not to detract from the "core" information; but I'll ask Klortho (or any other of the OAs) if these kinds of "History" sections are better near the beginning or near the end in Wiki articles. Jgould1400 (talk) 04:09, 3 May 2013 (U

The DSB section summarizes not just DSB but also differences between standard DSB repair pathway and NHEJ to help the reader understand why XRCC4 is important in NHEJ. It puts the whole article into context. We should clarify about the placement of the History section because the standard placement may be at the end of the article as Jim has it now. Thank you so much for reviewing our article! Cdunca12 06:14, 6 May 2013 (UTC)

Thanks again for your comments, Er1cah0p3. I think Cdunca has done a nice job on the DSB section and addressing your comments. As for the History section, no one has come back thus far with a recommendation or request to move it to the top, so we'll keep it where it is. Jgould1400 (talk) 08:44, 9 May 2013 (UTC)

Proposal for downsizing / migration

Sections "Double-stranded breaks" and "Mechanism", while expertly written, seem to me to contain way too much detail for an article about a specific protein in NHEJ pathway. I propose the following:

1) Use these sections to improve the DNA Damage Repair article ("Double-strand break" section). Alternatively, DSB section could also be expanded into an article on its own. This will help people who happen to learn about DSB from Xlf, Shieldin, Ku80 or other linked articles.

2) Reduce these sections to what's relevant here (a few sentences of intro), while expanding on the particular role of Xrcc4 (neither DSB nor VDJ sections even mention it).

Loard (talk) 06:55, 13 December 2019 (UTC)