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Tiny DNA circles are key drivers of cancer, study finds

med.stanford.edu

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Re: Tiny DNA circles are key drivers of cancer, study finds

#11
post #4

Earlier quoted context omitted.

Reading this gives me an understanding for how some of my friends feel when I talk about technology. “Make sure to set the dip switches on your SCSI drive and confirm your cable is USB 4+ PD.” Lol

English Wikipedia is a surprisingly good resource. https://en.wikipedia.org/wiki/SiDNA So these things interfere with genetic operations in the cell, including cancerous cells. There's some evidence linked showing they enhance cancer treatments. Radiotherapy works by inducing cell and DNA damage in cancer cells, and these siDNA hurt their ability to repair themselves. https://en.wikipedia.org/wiki/Extrachromosomal_ci…

Regarding plasmids, there is a similar mechanism of DNA exchange in human cells known as "gypsy transposons," that are viral fragments which were partially integrated into germline ancestry.

https://journals.plos.org/plosgenetics/article?id=10.1371/jo...

Re: Tiny DNA circles are key drivers of cancer, study finds

#12
post #7

The role of eccDNA in cancer is not a particularly new concept. However, studies like this are important to further elucidate cancer-promoting mechanisms. Additionally, the use of artificial eccDNA holds a lot of promise for genetic enhancement in many forms of life from humans, to livestock, to plants. Essentially, we could create artificial chromosomes which express useful genes or have inverted repeats which deliv…

Is this ecDNA of similar size to the circular DNA of the mitochondria? This seems like a reversion of the form of DNA to a prokaryotic state.

It ranges from much smaller to much larger than mitochondrial genomes.

https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA

> Extrachromosomal circular DNA is derived from chromosomal DNA, can range in size from 50 base pairs to several mega-base pairs in length, and can encode regulatory elements and full-length genes. eccDNA has been observed in various eukaryotic species[2][3][4][5][6][7][8] and it is proposed to be a byproduct of programmed DNA recombination events, such as V(D)J recombination.

There are basically two ways to keep DNA from degrading in the cell: protect the ends with special proteins or DNA structures, or make it so that there are no ends to protect by having the DNA be circular.

https://en.wikipedia.org/wiki/Linear_chromosome

> Linear chromosomes are not limited to eukaryotic organisms; some prokaryotic organisms have linear chromosomes as well.

> a good number of eukaryotic species do harbor linear mtDNA , some even broken into multiple molecules

Re: Tiny DNA circles are key drivers of cancer, study finds

#13
post #11

Earlier quoted context omitted.

English Wikipedia is a surprisingly good resource. https://en.wikipedia.org/wiki/SiDNA So these things interfere with genetic operations in the cell, including cancerous cells. There's some evidence linked showing they enhance cancer treatments. Radiotherapy works by inducing cell and DNA damage in cancer cells, and these siDNA hurt their ability to repair themselves. https://en.wikipedia.org/wiki/Extrachromosomal_ci…

Regarding plasmids, there is a similar mechanism of DNA exchange in human cells known as "gypsy transposons," that are viral fragments which were partially integrated into germline ancestry. https://journals.plos.org/plosgenetics/article?id=10.1371/jo...

So retroviruses literally integrated into our biological processes and became physiological? That's seriously awesome.

https://en.wikipedia.org/wiki/Retrotransposon

> An endogenous retrovirus is a retrovirus without virus pathogenic effects that has been integrated into the host genome by inserting their inheritable genetic information into cells that can be passed onto the next generation like a retrotransposon.

> When the retroviral DNA is integrated into the host genome they evolve into endogenous retroviruses that influence eukaryotic genomes.

Re: Tiny DNA circles are key drivers of cancer, study finds

#14

The role of eccDNA in cancer is not a particularly new concept. However, studies like this are important to further elucidate cancer-promoting mechanisms. Additionally, the use of artificial eccDNA holds a lot of promise for genetic enhancement in many forms of life from humans, to livestock, to plants. Essentially, we could create artificial chromosomes which express useful genes or have inverted repeats which deliv…

You are right. In the same issue there is also a paper from Andreas Beyer’s team on the effects of aging on faster error-prone transcription in several species.

Age-related difference (interpreted naturally as transcription errors) cut out the wrong pieces of precursor mRNAs and this can lead to RNAs and circular RNAs in the cytoplasm. Not to mention strange mRNA isoforms. Probably not a good thing.

K. Mozhui and others have shown an increase is epigenetic noise with age in mice and there is similar work in “wild” human cohorts.

But the key questions in all of this work are—-What is causal? What is just consequence?

The multiple flows of causality is a very tricky problem. Genetic variants are the most obvious candidates once environmental factors (radiation exposure, toxins, diet) are reduced or standardized in a well controlled laboratory environment.

Re: Tiny DNA circles are key drivers of cancer, study finds

#17
post #6

if you are a cancer researcher, please share research assumptions that are debunked yet still commonly held. i’m compiling a list. these must be empirically supported. for instance, i believe negative conclusions based on knockout studies are misleading, but this is not empirically proven and would not qualify. (if you knock out a fire alarm and the house still functions, saying the alarm serves no purpose is flawed.…

Levin, M. (2021), "Bioelectric Signaling: Reprogrammable Circuits Underlying Embryogenesis, Regeneration, and Cancer", Cell [1] is a general overview how cancer is a breakdown in communications leading to a down-scale of the self for the affected cell, see also Levin, M. (2021), "Bioelectrical approaches to cancer as a problem of the scaling of the cellular self", Progress in Biophysics and Molecular Biology [2]; for more articles [3].

In video format: "Why don't (today's) Robots get Cancer" [4]

[1] https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2900...

[2] https://www.sciencedirect.com/science/article/abs/pii/S00796...

[3] https://drmichaellevin.org/publications

[4] https://www.youtube.com/watch?v=L43-XE1uwWc

Re: Tiny DNA circles are key drivers of cancer, study finds

#18
post #11

Earlier quoted context omitted.

Regarding plasmids, there is a similar mechanism of DNA exchange in human cells known as "gypsy transposons," that are viral fragments which were partially integrated into germline ancestry. https://journals.plos.org/plosgenetics/article?id=10.1371/jo...

So retroviruses literally integrated into our biological processes and became physiological? That's seriously awesome. https://en.wikipedia.org/wiki/Retrotransposon > An endogenous retrovirus is a retrovirus without virus pathogenic effects that has been integrated into the host genome by inserting their inheritable genetic information into cells that can be passed onto the next generation like a retrotransposon. > W…

I read recently that DNA transcription for protein expression is able to identify and skip an inserted element, but that the protein will be slightly different at the boundaries.

It appears to have gone badly wrong for the "Tasmanian Devil."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802805/

https://www.science.org/content/article/origin-tasmanian-dev...

Re: Tiny DNA circles are key drivers of cancer, study finds

#19
post #7

The role of eccDNA in cancer is not a particularly new concept. However, studies like this are important to further elucidate cancer-promoting mechanisms. Additionally, the use of artificial eccDNA holds a lot of promise for genetic enhancement in many forms of life from humans, to livestock, to plants. Essentially, we could create artificial chromosomes which express useful genes or have inverted repeats which deliv…

Is this ecDNA of similar size to the circular DNA of the mitochondria? This seems like a reversion of the form of DNA to a prokaryotic state.

Highly variable. In cancers they can be much larger. Mitochondrial circular DNA is about 16,600 basepairs. In comparison, in the paper below one example of a cancer-driven ecDNA is 1,260,000 basepairs (EGFRvIII). ecDNA were originally detected using cytogenetic light microscopic methods, hence the original bias toward large size.

Wikipedia article: https://en.wikipedia.org/wiki/Extrachromosomal_DNA

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334176/

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