DNA RNA INFORMATIONS: genomic code

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CANCER GENES - 'METHYL MAGNET'

Medical researchers have discovered a new type of mechanism causing cancer susceptibility, showing that tiny changes in some anti-cancer genes can act as magnets to attract modifying "biochemical tags", effectively switching them off and predisposing families to an increased risk of the disease.

The study and its findings are reported in the leading international journal Cancer Cell.

The researchers, from the University of New South Wales (UNSW), believe a tiny spelling mistake involving a single letter in the DNA sequence near the start of the genes is what attracts the biochemical tag – known as methylation.
This biochemical tag directly impacts on our DNA, by switching genes off.
"Methylation sits on top of our DNA, and provides the instructions to turn the gene off," explains study co-leader, Dr Megan Hitchins, from UNSW's Lowy Cancer Research Centre.
In one well-known cause of hereditary cancer, changes in the cancer-prevention gene MLH1 are passed from parent to child creating up to 80 percent risk of developing bowel, uterine and other cancers. However, some families with hereditary cancer have no spelling mistakes in MLH1, but instead have methylation sitting on the gene.
"When the methylation attaches to the MLH1 gene in these families, it causes it to be completely switched off and as a consequence cancer develops," says study co-leader and head of the adult cancer program at the Lowy Cancer Research Centre, Professor Robyn Ward. "But until now, we did not understand how these methylation tags were being passed from parent to child."
In the study the researchers looked at three generations of a large family, who had cancer at a young age, but in whom no spelling mistakes typical of this hereditary cancer syndrome had been found. Strikingly several members of the family from all generations had methylation tags on their gene.
"In this family, biochemical tags attached to the MLH1 gene were present in all three generations. This was intriguing since these markers are usually removed during the production of eggs and sperm," Dr Hitchins said.
"What we found was that a subtle change near the gene was acting like a magnet to attract methylation. So it was not the methylation itself that was being passed from parent to child, but rather the DNA change, and this acted as a methyl magnet," she said.
The methylation was cleared away in the sperm and eggs and then recreated in each new generation, the researchers said.
Professor Ward said the discovery pinpointed the cause of cancer in this family and it offered new options for genetic diagnosis, counselling and early interventions in other families at risk of hereditary cancers.
The team is also exploring the use of certain drugs to clear away the methylation in cancer to switch the anti-cancer genes back on again. In the future these drugs may be used to create a more targeted approach to cancer treatment and possibly prevention.

UBC Scientists extracted dilluted and contaminated dna

University of British Columbia researchers have developed a new way to extract DNA and RNA from small or heavily contaminated samples that could help forensic investigators and molecular biologists get to “the truth.”
“By exploiting the physical traits of DNA – electric charge, length and flexibility – we’ve been able to extract DNA from samples that would otherwise not produce enough clean DNA for analysis,” says UBC Biophysics Prof. Andre Marziali.
The technique is being commercialized through Boreal Genomics, a UBC spin-off company, and is expected to have broad applications from basic life-science research to forensic sample analysis, bio-defence and pathogen detection for food safety and clinical diagnostics.
The research team, which includes scientists from UBC and BC Cancer Agency’s Genome Science Centre, details the technique in this week’s Proceedings of the National Academy of Science.
Extracting DNA by conventional methods – which rely on the molecules’ chemical properties – has proven challenging when there are only trace amounts of DNA or when the source sample has contaminants with similar chemical traits.
“We’ve found that DNA and RNA respond to electric fields in a way that is very different from other molecules,” says Marziali. “By exploiting this unique property, we were able to extract high quality DNA from a highly contaminated sample from the Athabasca oil sands.”
The team also successfully tested the technique on samples provided by the RCMP.
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GENOMIC CODE CRACKING - ATOMIC LEVEL GENE DECODING RESULTS

Hi... Today we seen some information regarding genomic code cracking that is atomic level gene decoding results that is revealed.Freinds Dr. Paul F. Agris, professor of biochemistry at NC State, and academic colleagues from England and Poland show clear evidence for 1966 “Wobble Hypothesis” offered by Francis Crick who was the co-founder of the DNA molecule and its double-helix structure, and Dr. Agris’ own “Modified Wobble Hypothesis” posed in 1991.

The scientists used x-ray crystallography of the cell’s protein-manufacturing unit, the ribosome, to provide a visual snapshot of the decoding process.

This research is published in the December 2004 edition of Nature Structural and Molecular Biology.

The Wobble Hypothesis was Crick’s attempt to make sense of how the cell decodes the genetic information of DNA – the molecule that constitutes all the genetic information in a cell – and then, from that information the biologically active proteins comes to an existence, Dr. Agris results.

The term DNA has 61 three-letter codes that are translated by transfer RNA (tRNA) into amino acids; also proteins are made of amino acids. But the facts is that there are only 20 natural amino acids. Squaring the disparity between the number of codes and the number of amino acids – there are three times as many codes as there are amino acids – became a hurdle for Crick and other early geneticists, Dr. Agris explanation.

Also Crick attempted to clear this hurdle with the Wobble Hypothesis. He based this theory on the first report of a tRNA molecule’s chemical structure discovered by Robert Holley in 1963. Normally, RNA molecules are composed of four nucleosides: adenosine, guanosine, cytosine and uridine (A,G,C,U). But the tRNA molecule which Holley studied included a modified nucleoside called inosine (I), Dr. Agris says. By seeing this inosine in an important area of the tRNA molecule – an area that read the three-letter DNA codes when the cell synthesizes proteins – led Crick to believe that a single tRNA used inosine to read more than one code, and that therefore the 61 codes were decoded by fewer than 61 tRNAs.

Example, Dr. Agris used the amino acid alanine, which has four codes. Crick’s hypothesis would allow that only the two tRNA molecules could be capable to decode all four alanine codes.By using the modified nucleoside I in place of A, G, C or U, one tRNA may be able to read three codes, effectively “wobbling” the reading.

Twenty-five years after the Wobble Hypothesis, Dr. Agris proposed his Modified Wobble Hypothesis. It stated that modified nucleosides other than inosine would in some cases expand tRNAs ability to translate codes by wobbling to greater numbers of three-letter codes, whereas other modified nucleosides would restrict the wobble to only one or two codes.

According to the recent paper,Dr. Agris and colleagues already proved that Agris’ alteration to Crick’s hypothesis was correct: Cellular modification of tRNA alters chemistry and also structure in a manner critical for tRNA to decode more than one three-letter code.

And by using atomic-level resolution – in which researchers can distinguish atom from atom – and working with a tRNA specific for the amino acid lysine,Dr. Agris and his colleagues show modified nucleosides enabling tRNA to decode genomic information on the ribosome, the cell’s protein synthesis machinery.

Thus Specifically, it shows modifications enabling the decoding of two codes. One modification acts like a platform on which decoding takes place, and the other allows a novel chemical and physical interaction to occur between tRNA and the code,Dr. Agris said.

“This is the first visualization that modifications are critical for decoding the genome through wobble,” Said by Dr. Agris.

Dr. Agris says that 15 to 20 percent of tRNAs in all organisms require modified chemistries in order for codes to be properly read and protein synthesis to be successful.

“An understanding of how modified nucleosides enable and improve wobble recognition of the three-letter codes for protein synthesis opens the possibility of using modified nucleosides to expand the cells’ use of tRNA to make new proteins, or in new ways to target the protein synthesis machinery in pathogens,” Said by Dr. Agris.

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