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Telomere Shortening Section

The “Telomere Shortening” section says that only the lagging strand becomes shortened. This is FALSE. The RNA primer on the 5’ end of both the leading and lagging strands cannot be replaced and are dropped. The authors’ confusion likely came from reading a text that said leading strand replication proceeds without any issues. This simply refers to replication being able to proceed uninterrupted. It is not a reference to the telomeres. For DNA polymerase III to bind at the 5’ end of DNA, an RNA primer must be in place. This is true for both the leading and lagging strand. The RNA primers within the lagging strand are removed by DNA polymerase I but the primers at the 5’ end (either 5’ end) are not removed. They are eventually enzymaticly degraded and thus result in telomere shortening on BOTH strands. Additionally, this section has no citations and I don’t have the time to rewrite it. Can someone please take care of this? —Preceding unsigned comment added by Scootdive (talk • contribs) 23:39, 7 October 2009 (UTC)[reply]

Since the leading strand starts at an origin of replication in the middle of a chromosome, there should be no problem replacing the RNA primer of the leading strand with DNA. The first RNA primer synthesized to begin the lagging strand will eventually provide the necessary 3’ end for DNA ligase I to work and connect the lagging strand to leading strand. Also, the leading strand will continue elongating in the 3’ direction until it reaches the 5’ end of the template DNA. I think you might be confusing the terminology of parent (template) vs. daughter strands, and lagging vs. leading (the two daughter) strands. There are two lagging strands and two leading strands per replication bubble. One of each combine to form one new daughter strand. Only the 5’ end of each daughter strand (the lagging strand end) will have the shortening problem. You are correct that there are two sites for telomerase action per DNA molecule, one on each 3’ end of template DNA. However, this telomere lengthening allows the lagging strands on either end to lengthen.

Also, DNA polymerase III and DNA polymerase I are prokaryotic polymerases, which would not be involved in eukaryotic replication. Only eukaryotes have telomeres and telomerases since their DNA is not circular. Cmcnicoll (talk) 01:03, 30 October 2009 (UTC)[reply]

Use of the term "Assay"

I changed the heading "Telomere Length Assay" to "Measurement of Telomere Length in the Laboratory", because it is my experience that the lay public is not familiar with the term "assay." —Preceding unsigned comment added by 208.59.168.214 (talk) 23:43, 29 April 2009 (UTC)[reply]

Telomere attrition by magnesium deficiency

Someone more skilled in editing Wiki articles than I needs to add the recent observation by David Killilea and Bruce Ames that magnesium deficiency (long known to accelerate aging) causes telomere attrition. Their abstract reads:

"Magnesium inadequacy affects more than half of the U.S. population and is associated with increased risk for many age-related diseases, yet the underlying mechanisms are unknown. Altered cellular physiology has been demonstrated after acute exposure to severe magnesium deficiency, but few reports have addressed the consequences of long-term exposure to moderate magnesium deficiency in human cells. Therefore, IMR-90 human fibroblasts were continuously cultured in magnesium-deficient conditions to determine the long-term effects on the cells. These fibroblasts did not demonstrate differences in cellular viability or plating efficiency but did exhibit a decreased replicative lifespan in populations cultured in magnesium-deficient compared with standard media conditions, both at ambient (20% O2) and physiological (5% O2) oxygen tension. The growth rates for immortalized IMR-90 fibroblasts were not affected under the same conditions. IMR-90 fibroblast populations cultured in magnesium-deficient conditions had increased senescence-associated β-galactosidase activity and increased p16INK4a and p21WAF1 protein expression compared with cultures from standard media conditions. Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate age-related disease."

This article is in the Proceedings of the National Academy of Sciences, (PNAS April 15, 2008 vol. 105 no. 15 5768-5773.) which is online at: http://www.pnas.org/content/105/15/5768.abstract —Preceding unsigned comment added by Georgeeby (talk • contribs) 03:42, 11 July 2008 (UTC)[reply]

Telomeric interval?

What is a telomeric interval? Tmangray 23:46, 11 April 2007 (UTC)[reply]

5 to 3

what does "5' to 3'" mean?

It's how one describes the "direction" of a sequence of DNA bases. The 5 and 3 refer to specific atoms that are part of the deoxyribose sugar ring in the DNA's backbone; the phosphate links between two deoxyriboses connects the 5' carbon of one deoxyribose to the 3' carbon of the next one. I'd need to draw a diagram to explain it really clearly, but this is something that should be handled within the DNA article. Bryan Derksen

Here is a schematic:

3'-------------------------5'
<enzyme> -->
5'-------------------------3'

The enzyme works here from the 3' to the 5' end (each - represents a base pair). It moves along the 3'-5' direction polymerizing in the 5'-3' direction. All the polymerases that have been discovered polymerize in the 5'-3' direction. This is a very important point to remember if you want to develop a deeper knowledge of biology and the process of DNA replication (and RNA synthesis, because it follows the same rule except that the RNA transcript is made in the 5'-3' direction). Ashermadan

I already put the explanation in DNA. Did I get the direction right? phma

I remember reading speculations that telomere could cause problems with cloning since the DNA used would have already shorter telomere. I'm loathe to add that without having any source to cite, though.

Regarding telomere shortening as a time-delay fuse, the article currently states "These theories remain relatively controversial at this time.". Is that true? Could a reference be added to a paper arguing otherwise, or is it simply that the theory is very new and relatively untested? I'd love to here more detail about why it is controversial, others probably would too. Bmord 07:03, 7 January 2006 (UTC)[reply]

The article states that for most multicellular eukaryotes, telomerase is only active in germ cells. However, the reserve capacity hypothesis article linked in the references section asserts that some amount of telomerase exists in adult skin cells. Also, prior to 5 months of age, somatic cells in zygotes apparently also express telomerase. Could this be rephrased to something more correct? Thanks. Bmord 07:03, 7 January 2006 (UTC)[reply]

Heat Resistance +

"A side effect of the longer telomeres was an increased resistance to the effects of heat exposure. The reasons for that effect are unclear."

With the increase in global warming is this not an experimental aspect to explore on humans in Africa who die every day of heat related symptoms, as well as children left unattended during the summer that either die or experience life crippling afflictions? Depending on the true uses of such a new treatment, it would certainly be worth it to explore every possibility such a treatment would bring forth, would it not?

Reformatted --Chris 00:40, 8 July 2006 (UTC)[reply]

Misspelling on telemere page

The species Candida guilliermondii is spelled wrong, as guillermondii. This is especially a problem because elsewhere in Wikipedia Candida guilliermondii is classified under Pichia guilliermondii, which is an old usage, I believe. Makes it hard to look stuff up. It's not anywhere in the text, it's in the table of sequences. Richard8081 05:36, 17 July 2007 (UTC)[reply]

RNA in telomeres!

Here's a fascinating article: New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing. Someone should really read the original article and include some of that information here. Unfortunately, I'm a bit swamped at work. --Slashme 08:11, 8 October 2007 (UTC)[reply]

Running Out?

How many years can the telomers shorten until their completly gone? —Preceding unsigned comment added by 70.100.23.242 (talk) 00:21, 19 January 2008 (UTC)[reply]

That depends on how quickly the cell is dividing. I don't know enough about the speed of division of cells to give you an accurate answer though I think you will find it will vary widely. Skin cells, for example die and are replenished very quickly, whilst other cells such as neurone stem cells divide rarely (at least in adulthood).

131.111.1.66 (talk) 23:32, 7 November 2009 (UTC)[reply]

Tips of shoelaces

I first saw the metaphor of telomers as being like the tips of shoelaces in Science News.

Metaphors are common and useful in explaining science, in classes, magazines and textbooks.

I think the metaphor makes the function of telomeres easier to understand. I'm not sure what it takes away from the article -- perhaps people want the article to be serious and it's too mundane.

Can you tell me, SierraSciSPA, why you don't think it belongs in the article? I'm not insisting that it go in, but I just want to articulate a good reason, for the record. Nbauman (talk) 03:06, 30 January 2008 (UTC)[reply]

Well, for the record, I think the metaphor of telomeres to aglets is very questionable. Aglets have two main purposes: 1) to protect laces from fraying; and 2) to make laces easier to fit into holes. Telomeres have several known purposes, including: 1) to protect the ends of chromosomes; 2) to provide a disposable buffer for DNA polymerase, which cannot replicate a complete sequence of DNA; 3) arguably, to ensure that deletorious mutations will be only as long-lived as the Hayflick Limit and thus to reduce the incidence of cancer. Bottom line: while aglets and telomeres do certainly have one thing in common, it seems that the differences between them are far more significant than the similarities. I think drawing the comparison is more likely to mislead than to inform. I'm certainly not going to edit war over this point, but that's pretty much what I think of it.

That said, though, in general, I applaud your efforts to make this article more readable to a layperson. I myself *am* a layperson, and when I read it for the first time, I was completely bewildered. The article includes the sentence "during replication, DNA polymerase can only synthesize DNA in a 5' to 3' direction and can only do so by adding polynucleotides to an RNA primer that has already been placed at various points along the length of the DNA." How is any non-biologist supposed to be able to read that?? --SierraSciSPA (talk) 05:42, 30 January 2008 (UTC)[reply]

You're saying that we shouldn't use the metaphor that telomeres are like the tips of shoelaces, because telomeres share only one quality with shoelaces, but have many other qualities that they don't share with shoelaces.

I don't quite follow that. Science writers and teachers often use metaphors to get their ideas across, and the comparison usually shares only one point of description. For example, people compare the DNA molecule to a ladder, but a ladder has all kinds of qualities that DNA doesn't have. You can climb on a ladder, but you can't climb on a DNA molecule. Ladders are made of wood or metal, but DNA molecules are not. People compare the DNA molecule to a blueprint, but there are lots of differences between a literal blueprint and DNA.

Scientists use metaphors all the time, to explain and even to develop their ideas. They describe molecules as "gatekeepers". They compare a part of the brain to a sea horse, or a telephone exchange. Günter Blobel famously described his address tags to Zip codes. The Nobel Prize speeches are full of such metaphors.

Metaphors are a basic part of thinking. You can't be too literal and reject them. As you may know, one the symptoms of severe mental illness, such as Alzhemier's disease, is an inability to understand metaphors[1]. I'm not suggesting this is a problem here.<g> Nbauman (talk) 14:53, 30 January 2008 (UTC)[reply]

I'm not going to take a stance against all metaphors - but the two things being compared in a metaphor should at least share a primary purpose. DNA and a blueprint both contain instructions for structures; mitochondria and power plants both generate energy that will be used elsewhere. But the primary purpose of aglets is to protect the ends of something, and with telomeres I think that's only a secondary purpose - the primary purpose of telomeres is to enable the DNA polymerase to do its job, thus making replication possible. I almost want to argue that a telomere is more like copy machine toner than an aglet - that is, you need it to make copies, and it eventually runs out. Note, however, that I really don't want to say "telomeres are like copy machine toner" in the article :) --SierraSciSPA (talk) 16:37, 30 January 2008 (UTC)[reply]

Relative brightness

Is the grey of the chromosomes and the bright white of the telomeres in the photo the result of emitted light, or stimulated (how?) emission, or variations in reflectance / transmission? bucksylBucksyl (talk) 17:22, 18 February 2008 (UTC)[reply]

I would presume the telomeres had been labelled with a fluorescent dye (possibly by attaching it to a telomere specific antibody) Hence when light of the correct wavelength hits the chromosomes the dye is excited and emit light of a different wavelength and the light is observed. This probably uses confocal microscopy-look it up if you want to know more.

For the record, the reason the chromosomes show up in gray is probably because the antibody is specific to a certain (repeating) sequence that is present in telomeres, but the sequence occasionally occurs in the DNA of the chromosome, hence resulting in a low level of illumination of the rest of the chromosome where the sequence is present.131.111.1.66 (talk) 23:44, 7 November 2009 (UTC)[reply]

While I can't be certain, what you are seeing in that image is almost certainly an image of fluorescent in situ hybridization (FISH) for telomeres. Cells are isolated while dividing and prepared such that the chromosomes remain intact. The solution containing chromosomes is then literally dropped onto glass slides (called a "metaphase spread"). In this case, the chromosomes are then hybridized with a fluorescently-labeled DNA or PNA probe that has a complementary sequence to the telomere. The chromosomes are stained with a DNA dye such as DAPI or Hoechst that fluoresces when bound to DNA (with different excitation and emission maxima than the fluorophore used to label the telomere probe). After all the processing, the chromosomes can be photographed using standard epifluorescence / wide-field microscopy (confocal is rarely used for metaphases since there is very little sample depth and an infrequent need for absolute colocalization of multiple signals). Each channel (the DNA dye, and the telomere probe) is stimulated and the fluorescence captured separately, and these can be merged into a multicolor image. What the picture here shows is simply a grayscale version of this multicolor image where the telomere signal, as it often is in metaphase FISH, is considerably brighter than the DNA dye. Sorry to throw all that out, but I figured I'd clarify - while immunofluorescence (detection with an antibody) can be used to find telomeres in metaphase spreads, it is uncommon because FISH is technically much simpler to perform. Dcteas17 (talk) 08:44, 9 November 2009 (UTC)[reply]

Wow.

Doesn't biology just blow your mind? —Preceding unsigned comment added by 79.68.146.250 (talk) 23:50, 3 March 2008 (UTC)[reply]

Only now and then. SteveD 10:59 am 30th May 2008. —Preceding unsigned comment added by 124.180.135.136 (talk) 01:00, 30 May 2008 (UTC)131.111.1.66 [reply]

Immortal butterfly

What you'll get if you will connect the ends of the X's? Eternity ;) Denis Tarasov (talk) 09:03, 2 June 2008 (UTC)[reply]

Telomere Shortening

During repeated cell division, do the telomeres of its chromosome shorten by a certain number of 6-nucleotide repeats (in the case of humans)? Is it predictable or random during each division? Will the chromosome not necessarily lose 6-nucleotide repeats, and lose say one and a half repeats? Adee08 (talk) 17:41, 28 July 2008 (UTC)[reply]

Ambiguity

Re: forensics, you can "determine the age of any forensic sample that contains well-preserved DNA." I find the sentence a bit ambiguous—what it really means is you could, for example, tell how old someone was from their DNA, right? It wouldn't tell you the age of the cell itself (it would tell you how many repetitions that cell represented from the initial birth of the organism), it wouldn't tell you the age of the sample (the sample could have died 20 years ago, the telomere length would not have changed), etc. It has a pretty specific "age" meaning here. I'm having trouble articulating a clearer version of this, but perhaps someone can do that. If I had a DNA sample of a 5 year old girl taken 20 years ago, the telomeres would tell me the sample was 5 years old, not 25 years old. If said girl was still alive, the sample would only be telling me how old the girl was when the sample was taken, not how old she is now. The sample itself was not 5 years old when it was taken—it just represents a cell which is five-years-removed from the birth of the organism. Right? --98.217.8.46 (talk) 22:24, 13 August 2008 (UTC)[reply]

References

It seems to me that there are at least some references in this article that aren't written in the usual "wikipedia manner" that most are, I'm thinking of mainly the first part of the "Human telomeres, cancer, and ALT." section, the references are written in brackets after the sentence, instead of with a link? I'm not sure if this is the way it's supposed to be after all, and I have no idea how to make them look right...so I figured someone experienced could do something about it, if it's possible.

Hannes, 83.255.65.145 (talk) 23:47, 6 March 2009 (UTC)[reply]

Biologists speculate a tradeoff between aging and cancer?

I think the line "Biologists speculate that this programmed death of potentially damaged cells reduces the likelihood of cancer but makes aging (and thus death) inevitable."

is too broad a generalization, and also, is not referenced. The article even later states that it is not even certain that telomeres cause aging:

"First, it is not even certain whether the relationship between telomeres and aging is causal. "

Also, programmed cell death (apoptosis) is not the same as cell "aging" or senescence.

For now I am going to remove the line as the issue of the cancer/aging trade off is better discussed later in the article.

Masparasol (talk) 23:53, 21 April 2009 (UTC)[reply]

What a shame!

Where is Nobel prize for Alexei Olovnikov? What a shame! —Preceding unsigned comment added by Vbg1975 (talk • contribs) 21:12, 5 October 2009 (UTC)[reply]

New research shows potential link with Omega 3

Should this be integrated?

" ... New research suggests the fatty acids may possess an even more fundamental benefit: Heart patients with high omega-3 intake had relatively longer "telomeres," which are stretches of DNA whose length correlates with longevity. ... "

http://online.wsj.com/article/SB10001424052748703837004575013393566949312.html

Cowicide (talk) 01:10, 20 January 2010 (UTC)[reply]

@@ Line 152: / Line 152: @@
 Where is Nobel prize for Alexei Olovnikov? What a shame!  <small><span class="autosigned">—Preceding [[Wikipedia:Signatures|unsigned]] comment added by [[User:Vbg1975|Vbg1975]] ([[User talk:Vbg1975|talk]] • [[Special:Contributions/Vbg1975|contribs]]) 21:12, 5 October 2009 (UTC)</span></small><!-- Template:Unsigned --> <!--Autosigned by SineBot-->
+== New research shows potential link with Omega 3 ==
+Should this be integrated?
+" ... New research suggests the fatty acids may possess an even more fundamental benefit: Heart patients with high omega-3 intake had relatively longer "telomeres," which are stretches of DNA whose length correlates with longevity. ... "
+http://online.wsj.com/article/SB10001424052748703837004575013393566949312.html
+[[User:Cowicide|Cowicide]] ([[User talk:Cowicide|talk]]) 01:10, 20 January 2010 (UTC)