Talk:Nucleotide excision repair

message: 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)
thread_title:  Merge [[Transcription-coupled repair|Transcription Coupled Repair (TCR)]] into NER 

message: Original Outline:
# Uvr Proteins
# Nucleotide Excision Repair in Eukaryotes
# Global genomic NER
# 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)
thread_title: Proposed Outline

message: 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 Kwok PY and Gu Z. Single nucleotide polymorphism libraries: why and how are we building them? Mol Med Today 1999; 5 538–543.Collins FS, Guyer MS and Charkravarti A. Variations on a theme: cataloging human DNA sequence variation. Science 1997; 278: 1580–1581..  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.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  A study of lung cancer cases found modest association between NER specific SNP polymorphisms and lung cancer risk.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  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)
thread_title: NER and Cancer

message: Two important genes in the NER pathway for which polymorphism has shown functional and phenotypic impact are the XPD and XPC genes 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.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..  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 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.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.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.  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 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) 47-55Blankenburg 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.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., especially in North Indian populations.Carl.d.martin (talk) 22:26, 15 November 2012 (UTC)
thread_title: NER Dysfunction result of DNA Polymorphism

message: 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)
thread_title:  Merge [[UvrABC endonuclease|UvrABC endonuclease]] into NER 

message: 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)
thread_title: Two questions from Aehall47

message: 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)
thread_title:  Final week mini-review