A DNA map with the blue-colored double helix, the green markers, and the starting points for copying the molecule in red. David Gilbert / Kyle Klein, CC BY-ND
April 25 is promising for biologists. It is DNA Day, reminiscent of the date in 1953, when scientists Francis Crick, Rosalind Franklin, James Watson, and Maurice Wilkins published important scientific papers describing the helical structure of the DNA molecule. On April 25, 2003, the conclusion of the Human Genome Project was announced. Now, the annual celebrations of this day celebrate the molecule of life with new discoveries. What a better time to get a new picture of DNA.
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I'm DNA DAVE (or at least my mark since 1
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For example, I would like to know where the process of DNA replication begins on each chromosome. The error-free duplication of DNA is essential for the production of healthy cells. If this process is incomplete or interrupted, it can lead to cancer and other diseases.
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In our image, this familiar double helix staircase is not visible, as that perspective is zoomed out – as if you look at the map of a country against a city. Each of these molecules corresponds to 50,000 spirals of the spiral staircase – an integral part of a human chromosome.
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Creating a DNA Map
This image, taken with a device called Bionano Genomics Sapphire Imager, shows single DNA molecules – stained blue, green, and red. These DNA strands were aligned by passing them through narrow tubes – called nanochannels – that correspond to only one piece of DNA. As the DNA slips into the tube, the strands will straighten up.
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The entire DNA molecule is colored blue and the green check marks are landmarks – or specific DNA sequences that occur on average every 4,500 base pairs. The pattern of landmarks provides a unique fingerprint that shows us where we are along a chromosome. The red fluorescent blips mark the places where the DNA started to replicate. These sites are referred to as "origins of replication" and are the place where the DNA is first unrolled so that the duplication process can begin.
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Researchers at Bionano Genomics in San Diego have developed this nanochannel technology to record regions of chromosomes that are otherwise non-mappable because difficult genetic sequences make sequencing difficult of the four bases. This device solved the problem by "looking" at the arrangement of sequences on a molecule and reading 30 billion base pairs in one hour – this corresponds to 10 human genomes.
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My team and that of Nick Rhind of the University of Massachusetts have recognized that this nanochannel technology would allow us to conduct an experiment that has never been done before was: map all sites where DNA is located Replication starts simultaneously on millions of individual DNA fibers.
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Before a cell can divide into two independent cells, the DNA must make a copy of itself so each cell gets a complete set of chromosomes. To understand how the genetic material is duplicated, it is important to know where along the chromosome the process begins. This has been the biggest challenge to investigate how replication of our own chromosomes occurs, and thus what goes wrong with so many diseases, such as cancer, where replication goes awry.
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DNA replication and cancer
The origins of replication were elusive, as they occur in many places on different molecules. Therefore, we have to look at individual DNA molecules to detect them. Although scientists have been able to see individual DNA molecules since the early 1960s, we could not tell where a molecule came from in the chromosomes, so we could not map anything.
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Kyle Klein, a Ph.D. Student in my lab, labeled live human stem cells with red fluorescent molecules that labeled sites where DNA replication was imaged using the Bionano device. These images were then superimposed on the blue and green DNA maps of the same DNA molecules.
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We expect this method to completely transform our understanding of the replication of human chromosomes. Furthermore, since most cancer chemotherapeutics and most carcinogens – or carcinogens – in our environment rely on replication DNA attacks, we expect this method to provide a quick and comprehensive test of how these chemicals disrupt DNA replication. We also hope that we can show how we can mitigate these negative consequences and how we can develop better and less toxic chemotherapies.
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David M. Gilbert, Professor of Molecular Biology, Florida State University  # p # 13_14 # ad skipped = NULL #
This article is being re-published under "Creative" commons license. Read the original article.
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