Elizabeth Blackburns Text Telomeres, 2nd Edition

Discussion of the 2009 Noble Prize in Medicine, focusing on substances that reduce telomere shortening by activating the human telomerase enzyme

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Elizabeth Blackburns Text Telomeres, 2nd Edition

Post Number:#1  Post by ofonorow » Sun Jan 11, 2015 10:42 am

I split this from another topic (Desperately Seeking Susan) and this new topic will discuss the book Telomeres, 2nd Edition, Edited by Titia de Lange, Vicki Lundblad, and Elizabeth Blackburn. http://www.amazon.com/Telomeres-Cold-Spring-Harbor-Monograph/dp/0879698101/ref=sr_1_3?ie=UTF8&qid=1421671514&sr=8-3&keywords=telomeres+blackburn

Here are my notes on the Titia De Lange, Vicki Lundblead, and Elizabeth Blackburn book TELOMERES (2nd Edition).

From Chapter 5, Modeling Cancer and Aging in the Telomere-Deficient Mouse (Chapter contributed by Wong (Harvard), Chang, and DePinho (Harvard).

After describing how mice null for the telomere transcription gene were created


Telomere length determination in mTerc -/- mice confirmed a steady decline in telomere length at a rate of approx 120 base pairs per cell division, a rate analogous to the attrition rate in primary human cells lacking detectable telomerase.


They developed mice with shorter and shorter telomeres to examine what happens near the "end game."

... revealed chromosomal end-to-end fusion with loss of telomere repeats at the junction , in accord with significant reductions in telomere length in this model.

Subsequent analysis established a link between telomere dysfunction and complex cytogenetic rearrangements, including non reciprocal translocations - a common feature of human cancer.

Subsequent random breakage will generate broken chromosomes in the daughter cells capable of fusing to other free chromosomal ends.. (me evolutioin?)

It appears that decline in telomere length, rather than absence of telomerase activity per se, is the most important parameter dictating chromosomal integrity ..

These results further highlight the fact that telomerase persevere genome stability primarily by maintaining telomere structure and averting (damage)...

The late generation mTerc -/- males experienced progressive marked testicular atrophy, stemming from apoptopic germ cell depletion, and ... Females showed a decrease in the number of oocytes on ovulation and impaired capacity of most fertilized embryos to progress beyond early development.

Reconstitution of telomerase activity in later-generation mTerc -1- mice increases telomere lengths preferentially at the shortest telomeres, and is associated with the striking rescue of pathologies associated with telomere dysfunction.
Owen R. Fonorow
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Re: Desperately Seeking Susan

Post Number:#2  Post by ofonorow » Wed Jan 14, 2015 4:15 am

Some interesting fodder from the Blackburn, et. al. book Telomeres,

Pg56
The telomerase elongation reaction requires only a primer, deoxtnucleotide triphosphates, Mg(2+) and telomerase. No high-energy cofactor such as rATP or rGTP is required

The telomerase processivity measured in vitro can be affected by reaction conditions such as temperature, ionic strength, and dGTP concentration.
Owen R. Fonorow
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Re: Desperately Seeking Susan

Post Number:#3  Post by gofanu » Wed Jan 14, 2015 10:47 am

I like that little "Mg2+" in there.

More evidence that you need to stick to the basics first for anything to work.

FRM

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Re: Elizabeth Blackburns Text Telomeres, 2nd Edition

Post Number:#4  Post by ofonorow » Mon Jan 19, 2015 7:01 am

The idea that the telomerase enzyme (if I understand this correctly) has both lysine and proline binding sites struck me as interesting, to say the very least.

Page 66 In section The Reverse=Transcription Domain in the Catalytic Center of Telomerase.


Residues important for nucleotide binding (lysine residue in Motif 1 and proline residues in Motif 2)


Some conserved residues in the RT (RNA Transcription) domain of the TERT (Telomerase Enzyme Reverse Transcription) also have a role in repeat addition processivity. For example, in (some bacteria or single cell organism) TERT, a residue substitution at position 813 of Motif C from leucine to tryosine was shown to increase repeat addition processivity.



Unfamiliar nomenclaure, especially the various protein designations, makes it hard understand some things. Telomerase has to be built (by RNA reverse transcription) and various proteins either accelerate or inhibit this process. (Usually telomerase is inhibited in most of our normal cells. So-called Telomerase Activation is an attempt to express TERT gene thus make telomerase via reverse transctipion.) And then there is the process of telomere repeat addition - lengthening telomeres - and various enzymes that speed or slow this process in various species have been studied. (Makes me hope there is an online adult study telomere course available.)
Owen R. Fonorow
HeartCURE.Info
American Scientist's Invention Could Prevent 350,000 Heart Bypass Operations a year


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