werner syndrome gene

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Ryang174mako
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Joined: Mon Sep 18, 2017 5:06 pm
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werner syndrome gene

Post by Ryang174mako »

hi, need help with a science project about genetics and ageing
the wrn gene from werners syndrome is a caretaker tumor suppressor which is a gene that prevents cancer by stabilizing the genome (preventing damage) but it is also capable of alternative lengthening of telomeres without telomerase via homologous recombination and can use this to immortalize cells lacking telomerase like humans.

all of these reasons are why when mutated it causes progeria.

my high school science teacher ( i am a senior so this question may be advanced) has asked us to design an expirament and predict results, I have already made my prediction and turned in my assignment. but I want to know the opinion of a few experts so I'm going to tell you my expirament and let you yell me what you think

( 1 ) wrn over expression immortalized cells lacking telomerase so I would add multiple copies of this gene to cause over expression and therefore immortalization. would this increase the rate of cancer even though it is a caretaker tumor suppressor, if yes why?

that's the first question and this is the second please answer them separately.

( 2 ) as with the first I will add extra copies of wrn to cause over expression but since wrn over expression also increases p53 ( a master tumor suppressor, extra copies of this gene made a mouse completely cancer resistant) I would therefore add more copies of p53 as well, would the p53 cancer resistance be overridden by the wrn gene over expression and cancer rates would still increase, if yes why?

thank you ahead for your response.
SciB
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Re: werner syndrome gene

Post by SciB »

Hi,

You have asked some rather complex questions and I will try to answer them in as clear and accurate a way as possible. Do keep in mind that research is still in progress on the role of Wrn in aging and carcinogenesis and the mechanism currently proposed may turn out to be wrong or incomplete in some aspects.

Wrn is a protein that has a DNA binding domain that allows it to interact with telomeres and apparently assist the DNA polymerase/telomerase in replicating the telomere region so that telomere shortening does not occur. If the Wrn gene is mutated as in Werner's Syndrome (WS) then aging is accelerated. This may be a result of loss of telomere function that protects the integrity of genes that prevent cell senescence.

Here's a good reference that talks about the role of Wrn in aging and carcinogenesis:

http://jcs.biologists.org/content/120/5/713

(1) If Wrn is over-expressed in cells they lose their natural tendency towards senescence and continue dividing. This is basically what happens in a tumor when the normal controls on cell division are disrupted by DNA mutations. Normally Wrn blocks a cell from becoming cancerous by interacting with p53 and inducing apoptosis, but if there is way more Wrn than p53, then the cell may overcome the programmed cell death and continue dividing.

(2) If you over-expressed both Wrn and p53, I would predict that the apoptosis signals would be regained and the cells would die. P53 mutations are very common in cancer cells, so having a lot more wild type p53 around should prevent any tendency of a cell to lose control of cell division.

Here's a good reference for the p53-Wrn interaction: http://cancerres.aacrjournals.org/content/65/4/1223

This is a really complicated area of molecular biology and I am not an expert in aging research. There will be a lot of data published in the scientific literature that turns out to be wrong and separating out the truth is the goal of science. I hope you go on to make a career in research since you are seriously interested in figuring out why cells go bad and how to prevent it.

Please post again if we can help with analysis or evaluation of your proposal.

Good luck!

Sybee
Ryang174mako
Posts: 13
Joined: Mon Sep 18, 2017 5:06 pm
Occupation: Student

Re: werner syndrome gene

Post by Ryang174mako »

wrn increases p53 levels when overexpressed would that fact change based on the level of over expression for example 2 to 100 fold overexpression.
SciB
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Joined: Fri Feb 01, 2013 7:00 am
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Re: werner syndrome gene

Post by SciB »

Over-expressing Wrn will affect p53 levels but how much is going to depend on how the experiment is done--what kind of organism is used in the study. Mice will probably give a different result from humans and cells in culture don't respond the same way as cells within a body.

The only way to answer your questions would be to do a full literature search and make a final judgment based on the strongest and most consistent data. Since you are not running experiments you have to use other people's data and that always carries an inherent risk of error or misinterpretation. Scientists have biases just like other people and that's why publications are peer-reviewed to try and minimize the affects of bias, but it doesn't always work. So, be careful with the data you use and try to base your conclusions on the best papers which are usually ones that are published in the most reputable journals like Science, Nature, Cell, PNAS, PLoS1, etc.

I'm sure you did a good job in writing the research proposal. Let us know how you made out and if you want to pursue this line of research. If you can get taken on as a student volunteer in a university research lab then you could do some experiments where you have control over the variables and the interpretation and that is way more satisfying than hashing over someone else's data.

Good luck!

Sybee
Ryang174mako
Posts: 13
Joined: Mon Sep 18, 2017 5:06 pm
Occupation: Student

Re: werner syndrome gene

Post by Ryang174mako »

thank you again for your response.

how much doesn't really matter. what I'm asking is if wrn over expression increases p53 will over expressing wrn way above the level tested in that expiramwnt change that result like wrn will decrease p3

for example if we know that wrn increases p53 at 2 fold over expression is it then possible for wrn to inhibit p53 at a much Higher (100 fold) or lower (.5 fold) overexpression level.
SciB
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Posts: 2067
Joined: Fri Feb 01, 2013 7:00 am
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Project Due Date: n/a
Project Status: Not applicable

Re: werner syndrome gene

Post by SciB »

What I meant was that it matters what type of organism is used in the experiment. I don't see how you can get an answer to a speculative question like that unless you define what the experimental conditions will be.

If you are interested in studying this area you could contact someone at a university who does research with Wrn and ask them what would happen in a defined system where Wrn was deliberately over-expressed.
Ryang174mako
Posts: 13
Joined: Mon Sep 18, 2017 5:06 pm
Occupation: Student

Re: werner syndrome gene

Post by Ryang174mako »

thank you for your help, I really appreciate it! :D
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