Talk:Nucleotide excision repair

07/14/2011 - features added
I am 95.233.175.71 and i added the correct links to CSA and CSB genes in the "Nucleotide Excision Repair in Eukaryotes" section. I have updated a previous note by the user SmackBot who noticed that those two links were broken and thus added a pair of "" tags.

P.S.:(thinking it was necessary, i also added the links to the CSA and CSB genes in the respective disambiguation pages as well, which did not previously contain links to them; i wanted a place to write this, although it's not a matter concerning this particular page)

Merge Transcription Coupled Repair (TCR) into NER
As of November 2012, TCR is classified as an "other" form of DNA repair. However, TCR is a subpathway of NER. My group is hoping to make quite a few edits/expansions to this article, including the TCR section currently in NER. Once this occurs, it seems the information in the TCR article will overlap quite a bit with the TCR subsection in NER. To avoid this redundancy, should the TCR article be integrated with NER or remain a separate page? (I apologize for any breach of protocol; I'm still trying to get the hang of this!) Any guidance, opinions, etc would be greatly appreciated. Db4an (talk) 19:38, 6 November 2012 (UTC)

Proposed Outline
Original Outline:
 * 1) Uvr Proteins
 * 2) Nucleotide Excision Repair in Eukaryotes
 * 3) Global genomic NER
 * 4) Transcription coupled repair in Eukaryotes

Potential New Outline:


 * 1. NER in Prokaryotes
 * 1.1. Damage Recognition
 * 1.2. Dual Incision
 * 1.3. Repair & Ligation
 * 2. NER in Eukaryotes
 * 2.1. Damage Recognition
 * 2.1.1. Cooperative Binding
 * 2.1.2. Kinetic Proofreading
 * 2.2. Dual Incision
 * 2.3. Repair & Ligation
 * 3. Transcription Coupled Repair (TCR)
 * 3.1 Diseases Associated with TCR
 * 4. Global Genomic Repair (GGR) [currently Global genomic NER]
 * 4.1 Diseases Associated with GGR
 * 5. NER and Cancer
 * Subsections TBD
 * 5.1 NER Disfunction result of DNA Polymorphism
 * 5.2 Impact on Tumor Growth and Prognosis
 * 5.3 Potential for NER-related Therapeutic Targets

More information about our group's progress can be found on our project and talk pages! We would love any feedback, advice, edits, etc. Db4an (talk) 02:28, 13 November 2012 (UTC)

Proposed Test for NER and Cancer Portion
I have put together a first draft of the Cancer portion of our proposed layout and it appears below. I haven't had time to do much formatting, or put in all the links for other pages, and to the references yet, but I will be working on that soon. Once we institute the new layout on the NER page, we can copy this over. Carl.d.martin (talk) 22:26, 15 November 2012 (UTC)

NER and Cancer
Though historical studies have shown inconsistent results, genetic variation or mutation to nucleotide excision repair genes can impact cancer risk by affecting repair efficacy. Single-nucleotid polymorphisms (SNPs) and nonsynonymous coding SNPs (nsSNPs) are present at very low levels (>1%) in the human population. If located in NER genes or regulatory sequences, such mutations can negatively affect DNA repair capacity resulting in an increase likelihood of cancer development. While the functional impact of all polymorphisms has not been characterized, some polymorphisms in DNA repair genes or their regulatory sequences do induce phenotypical changes and are involved in cancer development. A study of lung cancer cases found modest association between NER specific SNP polymorphisms and lung cancer risk. The results indicate that some inherited polymorphic variations in NER genes may result in predisposition to lung cancer, and potentially other cancer states. Carl.d.martin (talk) 22:26, 15 November 2012 (UTC)

NER Dysfunction result of DNA Polymorphism
Two important genes in the NER pathway for which polymorphism has shown functional and phenotypic impact are the XPD and XPC genes. XPD, also known as ERCC2, serves to open DNA around the site of damage during NER, in addition to some other transcriptional activities. Studies have shown that polymorphisms at Exon 10 (G>A)(Asp312Asn) and Exon 23 (A>T)(Lys751Gln) are linked with genetic predisposition to several cancer types. The XPC gene is responsible for a protein which recognizes DNA during the early portion of the NER pathway. This gene can have polymorphisms at Intron 9 and SNPs in Exon 15 which have been correlated with cancer risk as well. Research has shown that a biallelic poly (AT) insertion/deletion polymorphism in Intron 9 of XPC is associated with increased risk for skin, breast and prostate cancers , especially in North Indian populations.Carl.d.martin (talk) 22:26, 15 November 2012 (UTC)

Impact on Cancer Prognosis
The study of a hereditary cancer, xeroderma pigmentosum has helped identify several genes which encode proteins in the NER pathway, two of which are XPC and XPD. XP is caused by a homozygous deficiency in UV DNA damage repair which increases the patients’ risk of skin cancer by 1000-fold. In heterozygous patients, the risk of cancer is sporadic but can be predicted based on analytical assessment of polymorphisms in XP related DNA repair genes purified from lymphocytes. In a study relapse rates of high-risk stage II and III colorectal cancers, XPD (ERCC2) polymorphism 2251A>C was significantly correlated with early relapse after chemotherapeutic treatment. Studies have indicated that the effects of polymorphic NER genes is additive, with greater frequency of variants, greater cancer risk presents  Carl.d.martin (talk) 22:25, 15 November 2012 (UTC)

References
 * 1. Kwok PY and Gu Z. Single nucleotide polymorphism libraries: why and how are we building them? Mol Med Today 1999; 5 538–543.
 * 2. Collins FS, Guyer MS and Charkravarti A. Variations on a theme: cataloging human DNA sequence variation. Science 1997; 278: 1580–1581.
 * 3. B Karahalil, VA Bohr and DM Wilson III. Impact of DNA polymorphisms in key DNA base excision repair proteins on cancer risk.  Human and experimental toxicology; 2012 31(10) 981-1005
 * 4. Lori C Sakoda1,2, Melissa M Loomis1, Jennifer A Doherty1,2, Liberto Julianto1, Matt J Barnett1, Marian L Neuhouser1, Mark D Thornquist1, Noel S Weiss1,2, Gary E Goodman1, Chu Chen1,2,3. Germ line variation in nucleotide excision ::repair genes and lung cancer risk in smokers.  Int J Mol Epidemiol Genet.  2012; 3(1): 1-17
 * 5. Pastorelli R, Cerri A, Mezzetti M, Consonni E, Airoldi L. Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes. Int J Cancer 2002;100:9-13.
 * 6. Hou SM, Falt S, Angelini S, Yang K, Nyberg F, Lambert B, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and ung cancer risk. Carcinogenesis 2002;23:599-603.
 * 7. Wang M, Gu D, Zhang Z, Zhou J, Zhang Z. XPD polymorphisms, cigarette smoking, and bladder cancer risk: A meta-analysis. J Toxicol Environ Health 2009;72:698-705.
 * 8. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, et al. XPD polymorphisms: Effects on DNA repair proficiency. Carcinogenesis 2000;21:551-5.
 * 9. Mittal RD, Mandal RK. Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population.  Indian Journal of Human Genetics 2012; 18(1) 47-55
 * 10. Blankenburg S, Konig IR, Moessner R, Laspe P, Thoms KM, Krueger U, et al. Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: A case-control study.Carcinogenesis 2005;26:1085-90.
 * 11. Shore RE, Zeleniuch-Jacquotte A, Currie D, Mohrenweiser H, Afanasyeva Y, Koenig KL, et al. Polymorphisms in XP and ERCC2 genes, smoking and breast cancer risk. Int J Cancer 2008;122:2101-5.
 * 12. Qiao Y, Spitz MR, Guo Z, Mohammad H, Lawrence G, Kenneth KH, et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res 2002;509:165-74.
 * 13. Ming-Yii Huang1,2,3, Wei-Yu Fang4, Su-Chen Lee5, Tian-Lu Cheng6, Jaw- Yuan Wang*7,8 and Shiu-Ru Lin*4 ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study. BMC Cancer 2008 8(50) 1-13
 * 14. Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, Guo Z, Lei L, Mohrenweiser H, Wei Q. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001 Feb 15;61(4):1354-7.

Carl.d.martin (talk) 22:25, 15 November 2012 (UTC)


 * Hi, Carl. Rather than put this on the talk page, go ahead and insert it right into the article.  Be bold! Klortho (talk) 14:06, 16 November 2012 (UTC)
 * I see you put it into the article. Looks good! Klortho (talk) 02:07, 17 November 2012 (UTC)

Problem with characterization of dual incision
Some anonymous user put this on my talk page, so I thought I would copy it here:
 * There is an oversimplification brewing in your layout on NER, namely the notion that dual incision is characteristic of NER. Mismatch Repair, a second major subpathway of NER, proceeds via a single incision step rather than a double incision step.

-- Klortho (talk) 01:19, 22 November 2012 (UTC)


 * Hi, thank you so much for your feedback! We looked into this a little more, and our understanding is that mismatch repair is not a subpathway of NER. DNA mismatch repair (MMR) is an excision repair pathway, but it is separate from NER. As a result, we can't compare them. Base excision repair, mismatch repair, and nucleotide excision repair are the three main excision pathways, but they all have different characteristics and targets. MMR targets mismatched Watson-Crick base pairs while NER targets lesions caused by UV/oxidative damage. NER proceeds via dual incision, MMR uses singular excision.


 * This article talks briefly about the three excision pathways in the Introduction section. Please let us know if that makes sense or if we misinterpreted your point. Again, thank you! Db4an (talk) 17:16, 30 November 2012 (UTC)

Merge UvrABC endonuclease into NER
Since it seems that the Prokaryotic NER portion of this article is heavily reliant on UvrABC endonuclease, we are proposing that the UvrABC page be merged into the prokaryotic section on the NER page. This would reduce redundancy between the two pages and offer a more straight forward assessment of the data. Please discuss and we'll continue to work toward merging the articles. Carl.d.martin (talk) 15:31, 1 December 2012 (UTC)

Two questions from Aehall47
I noticed that there are images for both the GG-NER and TCNER. I really like the incorporation images to aid in the understanding of complex processes. I was wondering if you have considered including an image that outlines prokaryotic NER? Additionally, in the introduction to the topic the statement is made "nucleotide excision repair enzymes recognize bulky distortions in the shape of the DNA double helix." Could you elucidate on what is meant by these distortions or provide a more description that might make what you mean by bulky distortions clearer? Aehall47 (talk) 15:48, 1 December 2012 (UTC)

Final week mini-review
Hi, guys. Here's a final-week mini-review of your page. It is just a few random notes, that I jotted down while skimming the page, and is not intended as a comprehensive review.

This is a great article! I don't have any substantive criticisms. Good job!

Klortho (talk) 03:09, 10 December 2012 (UTC)