20 October 2015

Genome operations

Molecular biologists have learned how to correct DNA packaging errors

This approach could be revolutionary in the treatment of various genetic diseases in humans.

Molecular biologists from leading American universities – Baylor University Medical School, Stanford University, Harvard University, the Massachusetts Institute of Technology have developed a new method with which you can edit the genome. Or, as the authors themselves say, to do "operations" at the genome level, Infox reports.

The method is based on changing the packaging of DNA in chromosomes.

The length of the DNA molecule is about two meters, and such a huge structure is placed in a tiny chromosome in the nucleus of the cell. It is possible to achieve such compactness due to packaging. The packaging takes place in such a way that the DNA helix is wound on a complex of certain proteins, as on a coil. The number of bends exceeds ten thousand.

Recently, molecular biologists from the Baylor University School of Medicine managed to find out that anomalies in the packaging and twisting of DNA lead to various genetic diseases. Moreover, as studies have shown, twisting is determined by how the bases at the ends of the bends are combined with one of the DNA-binding proteins – the so-called "zinc fingers". In this case, the protein "zinc finger" CTCF.

"Zinc fingers" are a group of DNA-binding proteins. There is a characteristic domain in their structure, including two cysteine and one histidine residue. 

These amino acids interact with the zinc ion, and the polypeptide chain located between them forms a finger-shaped loop. Zinc fingers are transcription regulators, in other words, regulators of the gene.

In their current study, scientists have made a big step forward – they managed to show that by changing the sequence on the bends of DNA, it is possible to influence the very process of DNA stacking and the formation of bends.

"This means that it is theoretically possible to eliminate errors in DNA stacking, while not damaging neighboring areas in any way," says the study's lead author Dr. Erez Aiden, Erez Lieberman Aiden (in a press release, the Team at Baylor successfully performs surgery on a human genome, changing how it is folded inside the cell nucleus – VM).

To edit the DNA stacking, the authors used the so-called CRISPR system. This system is based on the Cas9 protein, which cuts the double-stranded DNA chain of the cell so that the desired segment can be inserted there. 

With the help of RNA guides, short guide sequences of RNA, geneticists have learned to show Cas9 the place where it is necessary to make an incision. 

(Picture from Rice University Gene on-off switch works like backpack strap – VM.)

"Using this system allowed us to work as if with a "genetic scalpel" and add or remove various small sections of the genetic code. These manipulations make it possible to change the DNA stacking, and precisely achieving the stacking that we need," says graduate student Suhas Rao.

"The CTCF protein works as a code that determines the twisting of DNA. Now that we have managed to unravel this code, we can control the entire process of DNA stacking," says Eric Lander, one of the authors of the study.

You can read more about the results of this study in the latest issue of the PNAS journal.

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