Common DNA mutation

In human DNA, guanine and thymine, are able to change shape in order to form an inconspicuous rung on the helical DNA "ladder." This allows them to survive by avoiding the body's natural defenses against genetic mutations.When these two bases form a hydrogen bond by accident, at first, they don't fit quite right," explained Zucai Suo, professor of chemistry and biochemistry at The Ohio State University and co-corresponding author of the study. They stick out along the DNA helix, so normally it's easy for the enzymes that replicate DNA to detect them and fix them. But once in a while, before they can be detected, they change shape.

The discovery provides a foundation for work on other types of DNA mutations, which are responsible for diseases as well as normal aging and evolution. The four bases of DNA each have their own size and shape, and are supposed to fit together in just the right way. Adenine (A) is always supposed to pair with thymine (T), and cytosine (C) is always supposed to pair with guanine (G). The two "Watson-Crick" base pairs, A-T and C-G, form the DNA sequences of all life.

However, if G were to somehow mispair with T, for example, that would be a mutation. In fact, the G-T mutation is the single most common mutation in human DNA. It occurs about once in every 10,000 to 100,000 base pairs-which doesn't sound like a lot, until its consider that the human genome contains 3 billion base pairs.

Though scientists had long speculated that the G-T mispair shape-shifted in order to resemble a normal G-C or A-T pair, researchers used a form of nuclear magnetic resonance imaging to reveal that these Watson-Crick-like G-T mispairs form in so-called "naked" DNA. Researchers used a DNA polymerase, an enzyme that replicates DNA, to insert a G-T mispair into a DNA strand. By stopping the chemical reaction at different times and analyzing the resulting DNA molecules, they were able to measure how efficiently the polymerase could form the G-T mispair.

Researchers discovered that the G and T bases would pair, but in a misshapen way that stuck out from the DNA helix. Then, in a fraction of a second, the bases would re-arrange their chemical bonds so that they could "snap" into the shape of a normal base pair and fool the polymerase into completing the chemical reaction.

The mutation's survival is a real feat, since it has to overcome a good bit of basic physics. Bases pair in a certain way because of how the protons and electrons in their atoms are arranged. Base pairing requires some amount of energy, and the easiest, most energy-efficient pairs to form are the "right" ones -- A-T and C-G. In effect, the G-T pair has to overcome an energy barrier to form and maintain itself. It turns out that when the G and T bases change shape, they make themselves more energy efficient, less efficient than a normal base pair, but efficient enough.
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DNA and RNA editing could heal many diseases

Scientists have discovered two gene editing techniques to fix mutations that cause diseases like cystic fibrosis and Duchenne muscular dystrophy. Both diseases, and about half all human genetic disorders, are caused by mutations in single letters in the human genome, in which an 'A' appears where there should be a 'B.'

The newly-developed gene editing systems can target the smallest units of human DNA or RNA to undo the mutation that causes cystic fibrosis. One system edits DNA in the genome itself, while the other targets RNA, which transports genetic messages for making proteins. The editing systems work in living cells, and if researchers can find ways to deliver them to human patients safely and effectively, they could be used to reverse the mutations that cause genetic diseases.

DNA and RNA contain four base components: adenine, thymine, guanine and cytosine. Cystic fibrosis is caused by an inherited genetic mutation that leads to abnormal mucus production in the lungs and digestive system. The thicker-than-normal mucus builds up in and blocks airways. It can be managed with breathing machines, inhalers and medications, but some affected by it will eventually need lung transplants. There is no cure for cystic fibrosis and it can be fatal.

Cystic fibrosis could be prevented or corrected if only there were a 'G' in the genome where the disease's victims have an 'A.' The new gene editing technologies could rewrite the part of the genome or its messenger that spells cystic fibrosis. The gene editing system is technically called the Adenine Base Editor, or ABE.

The ‘A’ in ABE is for ‘adenine,’ one of four chemical bases that are the smallest elements of our genomes. Adenine is always paired with thymine, and guanine is always paired with cytosine. ABE targets the ‘A,’ adenine, and rearranges its atoms to turn it into guanine. So, where there is an incorrect AT set of base pairs in the genome, ABE can reset it to a GC.

These genetic editors give scientists the remarkable ability to rewrite any mutated base pair in the genome. The gene editors are developments on the CRISPR technology which allows scientists to efficiently target and edit the genome.

RNA editing avoids interfering with the genome itself. Because RNA plays a communication role in humans, rather than being the fundamental genetic information itself, changes to it might be more flexible, and reversible.
However, RNA degrades over time, so the impermanence of changes to its component parts (called nucleoside bases) could be disadvantageous too.
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