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Archive - Nov 25, 2014


Link Found Between Transcription and Disease-Causing DNA Repeat Expansions

Researchers in human genetics have known that long nucleotide repeats in DNA lead to instability of the genome and ultimately to human hereditary diseases such as Freidreich's ataxia and Huntington's disease. Scientists have believed that the lengthening of those repeats occurs during DNA replication when cells divide or when the cellular DNA repair machinery gets activated. Recently, however, it became apparent that yet another process called transcription (see image), which is copying the information from DNA into RNA, could also been involved. A Tufts University study published online on November 20, 2014 in Cell Reports by a research team led by Dr. Sergei Mirkin, the White Family Professor of Biology at the Tufts School of Arts and Sciences, along with former graduate student Dr. Kartick Shah and graduate students Ryan McGuity and Vera Egorova, explores the relationship between transcription and the expansions of DNA repeats. It concludes that the active transcriptional state of a DNA segment containing a DNA repeat predisposes it for expansions. "There are a great many simple repetitive motifs in our DNA, such as GAAGAAGAA or CGGCGGCGG," says Dr. Mirkin. "They are stable and cause no harm if they stay short. Occasionally, however, they start lengthening compulsively, and these uncontrollable expansions lead to dramatic changes in genome stability, gene expression, which can lead to human disease." In their study, the researchers used baker's yeast to monitor the progress and the fundamental genetic machineries for transcription, replication, and repair in genome functioning. "The beauty of the yeast system is that it provides one with a practically unlimited arsenal of tools to study the mechanisms of genome functioning," says Dr.

How Environment and Oxidized Nucleotides Contribute to Several Human Diseases

Using a new imaging technique, NIH researchers have found that the biological machinery that builds DNA can insert molecules into the DNA strand that are damaged as a result of environmental exposures. These damaged molecules trigger cell death that produces some human diseases, according to the researchers. The work, published online on November 17, 2014 in Nature, provides a possible explanation for how one type of DNA damage may lead to cancer, diabetes, hypertension, cardiovascular and lung disease, and Alzheimer’s disease. Time-lapse crystallography was used by National Institute of Environmental Health Sciences (NIEHS) researchers to determine that DNA polymerase, the enzyme responsible for assembling the nucleotides or building blocks of DNA, incorporates nucleotides with a specific kind of damage into the DNA strand. Time-lapse crystallography is a technique that takes snapshots of biochemical reactions occurring in cells. Samuel Wilson, M.D., senior NIEHS researcher on the team, explained that the damage is caused by oxidative stress, or the generation of free oxygen molecules, in response to environmental factors, such as ultraviolet exposure, diet, and chemical compounds in paints, plastics, and other consumer products. He said scientists suspected that the DNA polymerase was inserting nucleotides that were damaged by carrying an additional oxygen atom. After the DNA polymerase inserts a damaged nucleotide into DNA, the damaged nucleotide is unable to bond with its undamaged partner. As a result, the damaged nucleotide swings freely within the DNA, interfering with the repair function or causing double-strand breaks. These steps may ultimately lead to several human diseases.