Wikipedia talk:United States Education Program/Courses/JHU MolBio Ogg 2013/Group 82H

Article selection discussion

Hi Cisilya. Any thoughts re article selection? Please let me know. Thanks, Jim Jgould1400 (talk) 00:42, 5 March 2013 (UTC)

Hi again Cisilya, In addition to point mutation/missense mutation, I'm very interested in XRCC4. Whaty do you think? Best, Jim Jgould1400 (talk) 07:05, 5 March 2013 (UTC)

Hi Cisilya. I saw your post from last night on my talk page asking about "point mutation" or "nick"? I've also suggested point mutation. Regarding "nick", this is only a stub so far, which I guess is okay, but I wanted to know your rationale on this (in particular, what would be some of the main topics in a "nick" article). What do you think about XRCC4? Please let me know. Since this is all due tomorrow, I'd like to choose a topic tonight so we have time to write up a good rationale tomorrow. Thanks, Jim. Jgould1400 (talk) 22:23, 5 March 2013 (UTC)

Hi Jim,

My apologies for the late entry for my unit 5 Wiki post on our project page. I just started a new job last week. I think writing an article for the XRCC4 protein will be a good choice. It's very specific and it covers the DSB repair pathway by non-homologous end joining which we read in the text. There are several components to this topic that we can write about such as the background for how double-stranded breaks can occur, the pathway for DNA repair for this type of damage, XRCC4 gene encoding the protein, protein structure, other proteins working in concert with XRCC4, schematics of the mechanism, expanding on the pathology section and describe how mutations occurring in different splice variants of this protein (and DNA sequences associated with these mutations) are the basis of specific diseases, experimental techniques used to determine mutations, protein homology and changes in function (not sure how involved you want to get).

Missense mutation would also be a good topic. This is a very well characterized topic and will have many review articles on it. The point mutation article has more content than missense mutation or XRCC4, so I would prefer for us to create from less information already posted by others than an article that already contains a lot of content and working around this.

Also, how would you like to split up the work? Should we divide up the sections?

Thanks, Cisilya Cdunca12 05:00, 6 March 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Missense mutation has already been chosen by someone. I don't think we can duplicate. Cdunca12 05:06, 6 March 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Yes, I also saw that missense is now taken. I found a bunch of recent XRCC4 refs -- some potentially linking XRCC4 to bladder cancer (2012 paper by Mittal et al.) and to HCC (hepatitis B-associated hepatacellular carcinoma) in Korea (2012 paper by Jung et al.). Jgould1400 (talk) 09:35, 6 March 2013 (UTC)

I added a section heading to your discussion here. Klortho (talk) 13:44, 6 March 2013 (UTC)

Hi Cisilya: Unless you disagree, I'll officially designate XRCC4 as our article. I'm now drafting a statement of our rationale for submission on our project page prior to 11:59 PM EST tonight. — Preceding unsigned comment added by Jgould1400 (talk • contribs) 01:30, 7 March 2013 (UTC)

Hi Jim - That sounds good. XRCC4 it is! I think following the style guide for gene and protein articles as described in unit 5 tutorial will be a good format. We can add more based on the content. Cdunca12 02:11, 7 March 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Hi Cisilya -- As you may have seen already, I have inserted the required "Statement of Rationale for Article Selection" into our project page. If you any revisions you want to make, I think you can simply use the "edit" button. I think this will be a very good article! Jgould1400 (talk) 04:23, 7 March 2013 (UTC)

Hi Jim - I just added on to the first paragraph in regards to authors who discovered the crystal structure of XRCC4. I also added two additional sources. Let's think about which sections we would like to do. Thanks! Cdunca12 07:38, 7 March 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

I'm flexible regarding sections. I note, however, that since I've worked over 20 years in the pharmaceutical field, my main expertise on an article like this will be on the clinical/pathology/therapeutic side and less so on the biochem. Jgould1400 (talk) 19:42, 7 March 2013 (UTC)

I think that is fine. I can cover the background info, gene, protein, interactions with other proteins involved in the pathway. We can add other areas as needed if we come upon something interesting through our readings. Thanks! Cdunca12 03:50, 8 March 2013 (UTC)

Week 7 Wiki Discussion - Starting Work on the Article

Hi Cisilya. I plan to work on the Week 7 assignment mostly today and tomorrow and not so much on the Wednesday due date. Please feel free to use my Sandbox for the assignment (the instructions say to select one team member's Sandbox). Jgould1400 (talk) 00:20, 12 March 2013 (UTC)

If you take a look at my Sandbox, you'll see that I've added a new section for working on the XRCC4 article and have inserted subsections for references, images, and an outline for the Article. I added about 12 references and also inserted a 10-point draft outline with some sub-points. Jgould1400 (talk) 06:00, 12 March 2013 (UTC)

Regarding specific ways to improve the XRCC4 Wikipedia, as discussed previously, 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 and a way to encourage other editors to contribute. 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). 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), the specific mechanism of the protein and other proteins involved in the pathway with a clear schematic, its location in the organelles in the cell and how it may be visualized, known mutations and diseases they cause, experimental techniques currently being used to study the protein, and to make it really complete, a history section on who discovered the protein. Taking the above parameters into consideration combining with citing excellent peer-reviewed references in an accurate and original way should bring this article into a GA level article. Jgould1400 (talk) 06:12, 12 March 2013 (UTC)

Further to my research on the clinical/pathological/therapeutic aspects related to XRCC4, I’ve found the following: references potentially linking XRCC4 to: bladder cancer (2012 paper by Mittal et al.); HCC (hepatitis B-associated hepatocellular carcinoma) in Korea (2012 paper by Jung et al.); association of functional polymorphisms of the XRCC4 gene with the risk of breast cancer (Zhou et al. 2012); polymorphisms in XRCC4 having a possible influence prostate cancer (Mandal et al. 2011); and the role of XRCC4 in carcinogenesis and anticancer drug discovery (Wu et al. 2008). Jgould1400 (talk) 21:15, 12 March 2013 (UTC)

Hi again Cisilya. Between this page and my Sandbox, I think I've hit the main assignment areas for our Wiki Week 7 assignment, but please check and please insert some images. Thanks, Jim Jgould1400 (talk) 21:21, 12 March 2013 (UTC)

Hi Jim - After doing some research, I was able to find one image for the mechanism of NHEJ. I contacted the author directly, Dr. Murray Francis. He has his own DNA repair website and he had made some changes of an image that he had obtained from a textbook. Sir proteins are included in the schematic, so I have to look for current articles to see if this is still valid. It appears the Sir proteins help to condense DNA and stabilize it for DSB repair. I am also trying to get permission from ASM for images that I'm interested in from an article in Molecular Cell Biology. I have also expanded on the article outline and ideas section on the article talk page. Hope they are ok. Thanks, Cisilya. Cdunca12 04:49, 21 March 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Good finds -- Thanks!! If you look at my personal "talk" page you'll some good suggestions from Keilana re dealing with figures (easiest if you find something you like that's already in Wikipedia Commons). Jgould1400 (talk) 04:55, 21 March 2013 (UTC) Jgould1400 (talk) 20:07, 5 April 2013 (UTC)

Weeks 8-9 Discussion - First Article Contribution

Hi Jim - I am currently working on the Lead and Protein Structure sections for the due date tomorrow. I will try to get as much done for these sections but will continue adding on on an ongoing basis. Not sure what you're working on - can you contribute more to the clinical sections (5-7)? Thank you. Cdunca12 00:21, 4 April 2013 (UTC)

Hi Cisilya -- You read my mind. I was about to send you the same message. I am deep into the drafting of subsections/paragraphs under the "Pathology" heading. At the moment, the "subsections" I'm drafting fall into the following categories: (i) general discussion of linkage between XRCC4 function (incl. impairment thereof, e.g., due to mutation) and pathology; (ii) known mutation and related pathology (sub-subsections include various types of cancer and hepatitis); (iii) association of polymorphisms with risk of cancer susceptibility, and as biomarkers for cancer screening and diagnosis; and (iv) potential treatments (including RNAi-mediated targeting of sequences in DNA repair gene messages to radiosensitize tumor cells in order to augment the use of radiation to treat cancer). Jgould1400 (talk) 01:19, 4 April 2013 (UTC)

Articles that I'm currently focusing on for the above-listed topics include:

• Wu CN, Liang SY, Tsai CW, Bau DT, The role of XRCC4 in carcinogenesis and anticancer drug discovery, Recent Pat Anticancer Drug Discov. 2008 Nov;3(3):209-19. Review. PMID 1899178. (Important Review for role of XRCC4 in cancer). • Dahm K, Role and regulation of human XRCC4-like factor/cernunnos, J Cell Biochem. 2008 Aug 1;104(5):1534-40. doi: 10.1002/jcb.21726. Review. PMID 18335491 (Important Review for role of XLF). • Jung et al., Polymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients with chronic hepatitis B: possible implications on survival, J Hepatol. 2012 Sep;57(3):621-7. doi: 10.1016/j. jhep.2012.04.039. Epub 2012 May 29, PMID 22659345 (Conclusion: Polymorphisms of DNA repair genes play a potential role in the development, progression, and survival of Korean HCC patients with chronic HBV infection). • Mahaney et al., XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair, Biochem Cell Biol. 2013 Feb;91(1):31-41. doi: 10.1139/bcb-2012-0058. Epub 2013 Feb 5. PMID 23442139. • Zhang et al, Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment, J Radiat Res. 2013 Mar 1;54(2):235-42. doi: 10.1093/jrr/rrs095. Epub 2012 Nov 7. PMID 23135157 • Zhou LP, Luan H, Dong XH, Jin GJ, Ma DL, Shang H, Association of functional polymorphisms of the XRCC4 gene with the risk of breast cancer: a meta-analysis, Asian Pac J Cancer Prev. 2012;13(7):3431-6. PMID 22994773. • Zheng Z, Ng WL, Zhang X, Olson JJ, Hao C, Curran WJ, Wang Y., RNAi-mediated targeting of noncoding and coding sequences in DNA repair gene messages efficiently radiosensitizes human tumor cells, Cancer Res. 2012 Mar 1;72(5):1221-8. doi: 10.1158/0008-5472.CAN-11-2785. Epub 2012 Jan 11. PMID 22237628. • Mandal RK, Singh V, Kapoor R, Mittal RD, Do polymorphisms in XRCC4 influence prostate cancer susceptibility in North Indian population?, Biomarkers. 2011 May;16(3):236-42. doi: 10.3109/1354750X.2010.547599. PMID 21506695. (XRCC4 and bladder cancer). • Mittal RD, Gangwar R, Mandal RK, Srivastava P, Ahirwar DK, Gene variants of XRCC4 and XRCC3 and their association with risk for urothelial bladder cancer, Mol Biol Rep. 2012 Feb;39(2):1667-75. doi: 10.1007/s11033-011-0906-z. Epub 2011 May 27. PMID 21617942. (linking XRCC4 to bladder cancer: “In conclusion, these findings suggest that XRCC4 (rs6869366) and XRCC4 (rs28360317) play a significant role in conferring risk for UBC and can be used as a marker for UBC screening. Simultaneously, we have reported that presences of these polymorphisms are not a risk factor for tobacco smoking induced UBC. Moreover, no associations of XRCC4 polymorphisms with recurrence free survival were observed in patients treated with BCG immunotherapy.”) Jgould1400 (talk) 01:38, 4 April 2013 (UTC)

Unit 9 Progress Report: Additions and insertions spanned 10 subsections. Numerous references were added to the footnotes, and some of the "old content" (pre-JHU) was corrected or deleted. Six new subsections added under the "Pathology" Section are as follows: (1) Cancer Susceptibility, (2) Pathologies Outside of Oncology, (3) Role of XRCC4 in V(D)J Rearrangement, (4) Potential Use of XRCC4 as a Biomarker for Cancer Screening and Diagnosis, (5) Radiosensitization of Tumor Cells, (6) Potential Role of XRCC4 in the Future Development of Therapeutics. At the moment, the subsection on cancer susceptability is the most developed. Within the pathology section, I think that the subsections on the "V(D)J rearrangement", "radiosensitization", and "Potential Role of XRCC4 in the Future Development of Therapeutics" have the most potential in terms of further enrichment over the next couple of weeks. Jgould1400

Hi Jim - The articles that I will be focusing on are listed below for sections 1 - 4, and I will follow the outline that we structured earlier on our project page. Thanks.

• Yurchenko, Vyacheslav, et al. (2006). "SUMO Modification of Human XRCC4 Regulates Its Localization and Function in DNA Double-Strand Break Repair". Molecular Cell Biology 26(5): 1786 - 1794. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430232/
• Mahaney et al., XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair, Biochem Cell Biol. 2013 Feb;91(1):31-41. doi: 10.1139/bcb-2012-0058. Epub 2013 Feb 5. PMID 23442139.
• Mittal RD, Gangwar R, Mandal RK, Srivastava P, Ahirwar DK, Gene variants of XRCC4 and XRCC3 and their association with risk for urothelial bladder cancer, Mol Biol Rep. 2012 Feb;39(2):1667-75. doi: 10.1007/s11033-011-0906-z. Epub 2011 May 27. PMID 21617942
• Hammel, M., et al., (2011), “XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair”, J Biol Chem 286(37): 32638-50. PMID 21775435. http://www.ncbi.nlm.nih.gov/pubmed/21775435
• Wu, Pei-Yu, et al., (2009), “Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4”, Molecular and Cellular Biology 29(11):3163. PMID 19332554.
• Mari, PO, et al., (2006), “Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4”, Proc Natl Acad Sci USA 103(49):18597-602. PMID 17124166.

• Andres et al., A human XRCC4-XLF complex bridges DNA, Nucleic Acids Res. 2012 Feb; 40(4):1868-78. Epub 2012 Jan 27. PMID 22287571 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287209/ • Zhou LP, Luan H, Dong XH, Jin GJ, Ma DL, Shang H, Association of functional polymorphisms of the XRCC4 gene with the risk of breast cancer: a meta-analysis, Asian Pac J Cancer Prev. 2012;13(7):3431-6. PMID 22994773 Cdunca12 13:46, 5 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Hi Cisilya -- I'm glad you're looking at Andres et al. Among the XRCC4-related articles that appear to be the most important/oft-cited, Andres et al. is the one that I haven't yet discussed (falls mainly in your section anyhow). WIth regard to XRCC4 interactions -- particularly with XLF, Lieber et al (Lieber MR, Lu H, Gu J, Schwarz K (January 2008). "Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune system". Cell Res. 18 (1): 125–33. doi:10.1038/cr.2007.108. PMID 18087292)Lieber MR, Lu H, Gu J, Schwarz K (2008). "Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune system". Cell Res. 18 (1): 125–33. doi:10.1038/cr.2007.108. PMID 18087292. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) has a great section on this (Lieber's section is entitled "The XLF:XRCC4:DNA ligase IV complex in NHEJ"). Best regards, Jim 76.117.152.51 (talk) 20:05, 5 April 2013 (UTC) Jgould1400 (talk) 20:09, 5 April 2013 (UTC)

Hi Jim - Thanks for the suggestions. I will certainly review them. I am going to summary the pertinent facts from the introductions of each article listed for the Lead section. I would like to delete the information that was previously on the XRCC4 article site (before your post). I think it would be better if we create a fresh article as the content and wording are awkward. Is this ok with you? Thanks. Cdunca12 01:52, 6 April 2013 (UTC)

Regarding the pre-JHU content, I've already made a couple of selected deletions and corrections, but I am doing it carefully -- "sentence-by-sentence" so to speak -- rather than wholesale deletions. More importantly, please don't yet delete any images or tables or graphs. I haven't made any definitive decisions yet on what to keep or delete in this respect, but I have found that adding images etc is ridiculously complicated on Wiki; so I'm hesitant to delete any of these yet -- at least until such time as we are confident we can add (and keep) new images. Not only are the mechanics of adding images on Wiki ridiculous, but in one case I actually took an image directly from WikiCommons (which is supposed to qualify it as safe and acceptable) but some editor came along and rejected it -- not because they had a specific problem -- but rather because he/she indicated that the fact that I got it from WikiCommons (and it was already on other Wiki pages) was not good enough! In fact, at the moment, I feel strongly enough about this that, if we have any image we want to add, I think we should have one of the editors add it in for us before we delete any of the existing images. Jgould1400 (talk) 05:04, 6 April 2013 (UTC)

Well said, Jim. I agree - let's keep everything that is currently there for now, especially the images. I think it was unfair what they did because images can be used multiple times based on different purposes and content. I thought about creating my own schematic based on the descriptions of the articles but this will be time consuming and may not be accurate. Let me think about this some more. Have a nice weekend. Cdunca12 15:16, 6 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Units 11 - 12 - Second Article Contribution

XRCCR Article Edits:

Hi Jim – I would like to make the following changes to our article in the next couple of days and through the weekend:

• Lead section -Clean up the second paragraph. Make the protein name consistent. Include a sentence mentioning how DNA damage (DSB) occurs incessantly and lack of repair leads to mutations, chromosome loss, and cell death to establish clearer notability. Mention details about mutations causing specific diseases instead of just “increased risk of cancer”. There is no citation for the last sentence on other species that contain XRCC4 (Boghog may have added this). -Expand on the proteins involved in NHEJ and the basic mechanism.

• DSB section -I will consider reducing information to make more concise as suggested by our reviewers.

• Structure section -I am going to add more details such as protein crystal structure image (the one you uploaded last time – was that removed?) and key residues in protein binding domains involved in interactions with other proteins in NHEJ.

• Role in DSB repair section -Section name needs to be changed to “Mechanism”. The Mechanism section after this one needs to be eliminated or certain information can be incorporated into the previous section. This section is already long, but originally I was going to include more specific protein-protein interactions involving the residues at the contact sites/domains. -NHEJ image – I need to look into the other proteins (Sir, Rad50, etc.) -A second subsection for mechanism of V(D)J recombination should be included as this is another major function of NHEJ.

• Post-translational modifications -Will look into this for the final contribution (unit 14). Cdunca12 00:34, 17 April 2013 (UTC)

Sounds good. Jgould1400 (talk) 02:15, 17 April 2013 (UTC)

Hi Jim - I have modified the lead section and re-organized the DSB and Mechanism sections. I'm also thinking about removing the images for the RNA expression in tissues graphs. We can do more research for these but I think they will be extraneous and is taking up room for other important images to come. What do you think? Cdunca12 06:53, 22 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

It's fine if you want to move the RNA expression graphs but please don't remove them. I don't want to be scrambling around near the deadline to add in images only to learn that we can't reintroduce the graphs even though they were once in there already. (This, unfortunately, was what I experienced last time). If you want to move these, then just move them to/towards the bottom of the page). Jgould1400 (talk) 02:08, 23 April 2013 (UTC)

Ok. I will leave them where they are right now. I will add an explanation for these graphs once I look more into the references. I will also add new information for the structure section and the V(D)J mechanism section.Cdunca12 00:23, 24 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Progress Report for Units 11-12

Here's the Progress Report that I posted 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) 03:59, 26 April 2013 (UTC)

1) Added new, sourced information for a complete description of the structural properties of XRCC4. Will continue to add to and modify this information. Also added new subsections for basic gene and protein properties, post-translational modifications and interactions. The interaction section further below will be moved here and combined. 2) Completely modified lead section for a more concise and thorough summary. 3) Re-organized DSB section into three subsections. 4) Modified wording and citations in several areas. 5) Read, considered, and responded to teammates and other editors' comments. Made minor adjustments. 6) Coordinated with teammate, Jim, through correspondence on Wikipedia improvements. Cdunca12 16:01, 29 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Unit 14 - Final Article Contribution

Hi Jim - I wanted to give you an update on what I am currently working on for the unit 14, final article contribution. I will be adding new, sourced information on the following:

• Properties - Gene and protein properties; Post-translational modifications; Interactions (moving Interactions section from below to the Properties section)

• Mechanism - V(D)J recombination

• Adding an image for the different subunits for the crystal structure of XRCC4.

Cdunca12 04:50, 6 May 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Hi Jim - I have added new sourced information under subsections Gene and Protein (content from NCBI) and Post-translational modifications. I have emailed two authors and one journal of the articles I've been reading to get their permission on image use from their article and website. Still waiting on that. If I don't hear back, we will just use what we already have. Thanks. Cdunca12 14:43, 8 May 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Unit 14 - Progress Report

Cdunca12

1. Added four new subsections: Gene and Protein; Post-translational modifications, Interactions, V(D)J Recombination.
2. Inserted new image: Interactions of XRCC4 in NHEJ.
3. Added two new pubmed references.
4. Modified lead section.
5. Corresponded with teammate, Jim; responded to other classmates' reviews and other editors; responded to teammates on the dephosphorylation and adenosine diphosphate pages; forwarded email to OTRS in regards to the new image I uploaded for Interactions of XRCC4 in NHEJ using ticket 2013051010001624. Image is in question about having a free license. The image was originally forwarded to me by the author, Murray Junop from McMaster University with permission to reuse. Cdunca12 00:15, 11 May 2013 (UTC)

Jgould14

Revised/supplemented several sections/subsections; added text and several references; searched for more information and to see if we’ve missed anything significant; and corresponded with teammate, reviewers, and other classmates whose pages I’m reviewing.Jgould1400 (talk) 09:33, 9 May 2013 (UTC). OA Keilana told me the article looks great. Jgould1400 (talk) 02:15, 10 May 2013 (UTC)