Talk:Non-homologous end joining

Untitled
This article was flagged for lack of citations today. I just wanted to point out that I'm in the process of editing this page, and I plan to add citations within the next few days. Amazinglarry 14:30, 17 May 2006 (UTC)

[Artemis/DCLRE1C]

Robert The comment "nuclease Artemis is required for hairpin opening and may also be involved in trimming damaged or non-homologous nucleotides" is trivializing a rather important protein. Artemis is probably the primary actor that introduces microdeletions into the genome, resulting in gradual corruption of the genetic code and over time "aging" due to genome dysfunction. Artemis is one of perhaps 4 exonucleases in the genome (the others include WRN, MRN and Apollo) as well an endonuclease. Nucleases have the ability to alter the genetic code (and in fact that is presumably a major use of Artemis in V(D)J-recombination rejoining. References for the activity of Artemis might include Pastwa & Blasiak, 2003 & Budman & Chu, 2005.

The basic principle is microdeletions lead to frame shifts, frame shifts lead to dysfunctional proteins (which is bad enough) and increased energy consumption (which is worse) due to need to recycle proteins which do not fold properly. I call this the "Energy Catastrophe Theory of Aging" (non-published in peer-reviewed literature but it fits with many of the proposed theories of aging). The use of energy resources to produce dysfunctional proteins results in a reduction of functional proteins and/or greater energy demands which cause the mitochondria to produce higher amounts of free radicals which in turn feedback into increased rates of double strand breaks which require even more error prone NHEJ to correct. Misfolded proteins that end up in the ER can trigger apoptosis so one will have gradual cell loss over time as NHEJ repair corrupts the cellular genomes.

Aging is in large part due to a gradual corruption of the genomic program in cells and Artemis is the lead actor in that process.


 * Hi Robert, it's nice to see that someone actually read this article after I spent some time expanding it! For a short encyclopedia article on NHEJ, I don't know if there really needs to be a major expansion on the section about Artemis.  A couple more sentences and other references wouldn't hurt though.  I could see a longer discussion on Artemis fitting in better in the article on V(D)J recombination, which is currently outdated and doesn't even mention Artemis.  Or perhaps you would want to put some of the material you mentioned above in an aging-related article?  If you decide to make any changes, please remember to keep in mind that original research is not allowed on Wikipedia (see WP:NOT), so other editors may object if you add a lot of information on your unpublished theory of aging. Amazinglarry 17:53, 21 June 2006 (UTC)

I removed the sentence "Many lower eukaryotes such as fission yeast (Schizosaccharomyces pombe) also use NHEJ more frequently than homologous recombination" because it's wrong, or at least completely misleading. In fact, S.pombe uses HR almost exclusively during G2 phase of the cell cycle, and NHEJ is used in G1 phase when it is impossible to repair DSB by HR because S.pombe is a haploid organism, so only one copy of each DNA segment is present in G1. So S.pombe hardly makes use of NHEJ at all, because S.pombe spends the the majority of its time in G2 and only about 10% in G1. This becomes quite obvious also when you compare mutants deleted for rhp51 or rad22 (HR defective), with mutants deleted for pku70 or lig4 (NHEJ defective) - the former are quite sick and highly sensitive to DSB agents, in contrast to the latter which have no growth defect and are basically insensitive to DSB agents, at least in cultures of vegetative cells. Check Ferreira and Cooper, 2004 if you want to see the data.

This is the 2nd best wikipedia article on NHEJ
The article for DNA repair protein XRCC4 has a more thorough explanation of NHEJ.

173.25.54.191 (talk) 20:22, 6 August 2013 (UTC)