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Medicine Science

Cambridge University Scientists Find Quadruple Helix DNA In Human Cells 67

Posted by samzenpus
from the twice-the-fun dept.
SternisheFan notes that scientists at Cambridge University have found four-stranded DNA in human cells for the first time. "If you've ever studied genetics in school or college, you'll know that the structure of DNA is a double helix. You likely know that DNA carries all of our genetic code. While traditionally we think of only double helix DNA, scientists from Cambridge University in England have made an interesting discovery. According to the researchers, a quadruple helix is also present in some cells and is believed to relate to cancer in some ways. According to the researchers, controlling these quadruple helix structures could provide new ways to fight cancer. The scientists believe the quadruple helix may form when the cell has a certain genotype or operates in a certain dysfunctional state. Scientists have been able to produce quadruple helix material in test tubes for years. The material produced is called the G-quadruplex. The G refers to guanine, which is one of the base pairs that hold DNA together. The new research performed at the University is believed to be the first to firmly pinpoint quadruple helix in human cells."
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Cambridge University Scientists Find Quadruple Helix DNA In Human Cells

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  • The Fifth Element!!!

  • by rak0ribz (672551) on Monday January 21, 2013 @11:40AM (#42647297)
    ...that "Guanine Quadruplex" works equally well as the name for either a band or a signature wrestling move.
  • All of this biologist type speak doesn't help regular people to understand how it can help cure cancer. It does seem like it could be targeted but what the hell is it and where does it come from? is it important? Or does it only cause cancer?

    • by Anonymous Coward

      It occurs most often in rapidly dividing cells; which whilst not limited to includes cancer cells.

      That's as far as the link goes as far as I can read.

    • by ZombieBraintrust (1685608) on Monday January 21, 2013 @12:02PM (#42647563)
      Wikipedia seems to indicate that these structures can form because of telomeres. Telomeres are sections of DNA on the end that repeat the same code d(GGTTAG). They prevent damage to DNA sections that hold genes. So they are important for preventing cancer. Basically the telemeres at each end can bond with each other to form these quadruplex.
    • by interkin3tic (1469267) on Monday January 21, 2013 @12:27PM (#42647873)
      They found it in dividing cells. Cancer cells divide, which is the problem, as that causes tumors. I'm assuming they used multiple cell lines, some cancerous and some not, and found it present more in cancer cells than in normal cells.

      It says they're also found in S phase cells, when the DNA is being replicated. This might contribute to cancer through genomic instability. There is a LOT of DNA to copy each cell cycle. The DNA polymerase is an impressive bit of evolved machinery, if each DNA base pair were the size of a railroad tie, the polymerase would be zipping along at a thousand miles an hour, copying the railroad tracks nearly perfectly as it does. It's also pretty good at catching its own mistakes. However, changes in the structure of DNA can cause a much higher frequency of errors in copying, and consequently, can increase the rates of mutation. It might skip copying a gene important for preventing the cell from dividing.

      Perhaps most importantly though, these structures being present more in cancer cells than in normal cells means they might be good targets for identifying cells that are cancerous. Perhaps we can find a drug that directly or indirectly destroys those structures when they are present in such a way that the cell itself will be killed. That would be far more targeted than current chemotherapy, which attacks all dividing cells.

      Big if of course. At this point, as far as published stuff goes, it's not yet to the point where it is going to lead to something useful in hospitals in the definite future.
    • Real biologist here (Score:5, Informative)

      by Anonymous Coward on Monday January 21, 2013 @12:36PM (#42647997)

      Some portions of DNA are rich in Guanine residues. There's been a theory kicking around that these bits could form into tetromeres, which would make the two DNA strands extra sticky to each other. A number of really wierd phenotypes, including werner's syndrome which causes premature aging, can come from the inaccurate unfolding of G rich regions. Likewise the telomeres, ie the ends of the DNA which essentially work as a division counter are G-rich. As such, if the accurate unfolding, stability or stickyness of the DNA in these regions is affected, the cellular behavior will change.

      The article went through using a phage library to build an antibody specific for 4 stranded DNA (NOT easy), which did not respond to 2-stranded DNA or RNA structures. They then looked at whether, when and where tetromeres could be seen in a bone cancer cell line. Oddly enough, the regions most likely to show these structures, the telomeres, didn't show tetromeres. These structures were seen when the cell was about to get ready to divide, which makes some sense, since the cell will have more DNA. (There's a fair bit of research currently going on to study DNA supercoiling- DNA is compacted down very tightly, yet almost all of it is accessible at any given time)

      As far as curing cancer, any time you can isolate behavior of cancer-only cells, you have the ability to create a drug to target that function. If these tetromeres are seen only in cancerous cells, then you can design drugs against them. Beyond that, the folding and unfolding of DNA is a pretty hot topic, since volumetric compression, read speeds and accuracy are astonishing compared to even the best hard drives on the market

  • by Anonymous Coward on Monday January 21, 2013 @11:52AM (#42647431)

    The first annual Obfuscated DNA Contest

  • "Scientists studying the quad-helix have already determined it is heavily implicated in the alcoholism gene."

  • by Wdi (142463) on Monday January 21, 2013 @12:11PM (#42647675)

    triple DNA helixes are also known, just to expand your horizon beyond what is simplified in highschool textbooks:

    http://en.wikipedia.org/wiki/Triple-stranded_DNA

  • by lawpoop (604919) on Monday January 21, 2013 @12:15PM (#42647723) Homepage Journal
    Wait wait wait wait--- you're telling me those New Age kooks who said we were going to add another strand in our DNA after 2012 were actually right!?!?!
  • What I got out of the article is that scientists found these structures and were able to image them but don't clearly understand what they do. It sounds like we'll have to mint a raft of Ph.Ds studying this until we understand what it does.

    I'd not saying its cool, it really is. But it'll probably be 5 years of study before we understand what/why/how these structures work and relate to cell (mis)function.

    Science onward!!!
    • by Biotech_is_Godzilla (2634385) on Monday January 21, 2013 @03:41PM (#42650101)

      Actually, the BBC article is very misleading when it comes to pretending that this is an amazing new discovery that this lab has intrepidly worked out from first principles. The head of the lab which produced this paper is a chemist who is big in the field (in that he makes a bunch of drugs that bind G4 DNA, and farms them out to biologists who test them in their cell lines which are defective in DNA repair) but G4 DNA is something that there's a lot of circumstantial biological evidence for.

      You can look at the sequence of DNA (known from the human genome project) and see where G4 structures are likely to form. You can make G4 quadruplexes from short DNA sequences in vitro and do biophysics on them to show how incredibly strongly they interact (hard to boil them apart, and you can measure this happening with a calorimeter). There's also a lot of evidence that G4 quadruplexes are a) necessary as a regulatory/structural feature of chromosomes and b) potentially very dangerous/ deleterious if you take away the proteins which allow cells to replicate across G4-forming sequences properly.

      The +5 comments above got a bit confused about why G4 DNA is found in great abundance in cancer cells. The reason for this is difficult to explain quickly, but basically: in a chromosome that's chilling out, and hasn't got much going on, G4-forming guanines are paired with their complementary cytosine residues to make a double helix. They therefore can't and won't form a quadruplex until you do something to them. What allows them to form quadruplexes is the act of DNA replication. In DNA replication the double helix is 'unzipped', forming two single strands of DNA, which are then used to make new strands, complementary to each of the single strands of old DNA. [wikipedia.org]

      It's the unzipping into single strands that frees up G4-forming sequences, which can then form a "knot" in the unpaired single strand of DNA by binding "sideways" to each other in the same single strand of DNA (i.e. intramolecularly) [wikipedia.org]. Someone above said this 'causes the DNA polymerase to make mistakes in replication'. What's most likely to happen (there's at least 2 strands of evidence for this) is the cell's normal replication machinery cannot deal with the G4, stalls and stops. It then waits around for ages for the G4 to be resolved. This is one cancer link - when the cell can't deal with the knot in a sensible period of time (hours), eventually the replication machinery 'gives up', the replication fork collapses, and you lose and rearrange DNA sequence, causing either massive cell death, or mutations and cancer in the few cells that do survive.

      The other link, though, is what the +5 comments were getting confused about above - cancer cells appear to have more of these G4 structures than normal cells. This is in no way surprising at all though - it's not about "having more DNA", or it's about having more replicating DNA. i.e. DNA that's in a single-stranded state, and that can therefore form G4 quadruplexes. Stem cells also show more G4 DNA, as they're replicating, and replicating fast, just like cancer cells.

      The 'making G4 drugs' idea comes from the same place that an awful lot of cancer treatments come from - these are fast-growing cells, and are therefore more susceptible to things that disrupt DNA replication, compared to normal cells which aren't replicating (most 'traditional' chemotherapy causes DNA damage, disrupting replication, and the main reason radiotherapy is thought to work is that it also causes DNA damage). If you drastically choke up DNA replication, you get some catastrophic cell death in fast-replicating cells, and if you can make a drug which only affects DNA replication without causing DNA damage, you can get the good effects of chemo without the bad (potential) effects of secondary cancers ten or fifteen years down the line (due to the massive dose of DNA damage you swallowed

      • by RDW (41497)

        "...(there's at least 2 strands of evidence for this)..."

        I see what you did there.

  • Get Patrick Stewart's wheelchair oiled up...

  • by Anonymous Coward

    Leloo dallas multipass.

  • (DNA = Douglas Noel Adams)

    Haggunenons have the most impatient chromosomes in the Galaxy. Whereas most species are content to evolve slowly and carefully over thousands of generations, discarding a prehensile toe here, [...] hazarding another nostril there, the Haggunenons would have done for Charles Darwin what a squadron of Arcturan Stunt Apples would have done for Sir Isaac Newton. Their genetic structure is based on the quadruple sterated octohelix....

If I have seen farther than others, it is because I was standing on the shoulders of giants. -- Isaac Newton

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