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Extra DNA a “spare tire” for genome?

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From ScienceDaily:

Carrying around a spare tire is a good thing — you never know when you’ll get a flat. Turns out we’re all carrying around “spare tires” in our genomes, too. Today, in ACS Central Science, researchers report that an extra set of guanines (or “G”s) in our DNA may function just like a “spare” to help prevent many cancers from developing. More.

The researchers scanned the sequences of known human oncogenes associated with cancer, and found that many contain the four G-stretches necessary for quadruplex formation and a fifth G-stretch one or more bases downstream. The team showed that these extra Gs could act like a “spare tire,” getting swapped in as needed to allow damage removal by the typical repair machinery. When they exposed these quadruplex-forming sequences to oxidative stress in vitro, a series of different tests indicated that the extra Gs allowed the damages to fold out from the quadruplex structure, and become accessible to the repair enzymes. They further point out that G-quadruplexes are highly conserved in many genomes, indicating that this could be a factory-installed safety feature across many forms of life.

Here’s the abstract:

Uncontrolled inflammation or oxidative stress generates electron-deficient species that oxidize the genome increasing its instability in cancer. The G-quadruplex (G4) sequences regulating the c-MYC, KRAS, VEGF, BCL-2, HIF-1a, and RET oncogenes, as examples, are targets for oxidation at loop and 5′-core guanines (G) as showcased in this study by CO3•– oxidation of the VEGF G4. Products observed include 8-oxo-7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), and 5-guanidinohydantoin (Gh). Our previous studies found that OG and Gh, when present in the four G-tracks of the solved structure for VEGF and c-MYC, were not substrates for the base excision repair (BER) DNA glycosylases in biologically relevant KCl solutions. We now hypothesize that a fifth G-track found a few nucleotides distant from the G4 tracks involved in folding can act as a “spare tire,” facilitating extrusion of a damaged G-run into a large loop that then becomes a substrate for BER. Thermodynamic, spectroscopic, and DMS footprinting studies verified the fifth domain replacing a damaged G-track with OG or Gh at a loop or core position in the VEGF G4. These new “spare tire”-containing strands with Gh in loops are now found to be substrates for initiation of BER with the NEIL1, NEIL2, and NEIL3 DNA glycosylases. The results support a hypothesis in which regulatory G4s carry a “spare-tire” fifth G-track for aiding in the repair process when these sequences are damaged by radical oxygen species, a feature observed in a large number of these sequences. Furthermore, formation and repair of oxidized bases in promoter regions may constitute an additional example of epigenetic modification, in this case of guanine bases, to regulate gene expression in which the G4 sequences act as sensors of oxidative stress. Open access – Aaron M. Fleming, Jia Zhou, Susan S. Wallace, Cynthia J. Burrows. A Role for the Fifth G-Track in G-Quadruplex Forming Oncogene Promoter Sequences during Oxidative Stress: Do These “Spare Tires” Have an Evolved Function? ACS Central Science, 2015; 150706102953001 DOI: 10.1021/acscentsci.5b00202

Just think: It all happened by the merest chance in an infinite multiverse parade! Or else … intelligence matters

See also:

Not only is earth one nice planet among many, but our entire universe is lost in a crowd

The multiverse: Where everything turns out to be true, except philosophy and religion

As if the multiverse wasn’t bizarre enough …meet Many Worlds

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