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Researchers show how cells' DNA repair machinery can destroy viruses
Date:1/21/2013

A team of researchers based at Johns Hopkins has decoded a system that makes certain types of immune cells impervious to HIV infection. The system's two vital components are high levels of a molecule that becomes embedded in viral DNA like a code written in invisible ink, and an enzyme that, when it reads the code, switches from repairing the DNA to chopping it up into unusable pieces. The researchers, who report the find in the Jan. 21 early edition of the Proceedings of the National Academy of Sciences, say the discovery points toward a new approach to eradicating HIV from the body.

"For decades, we've seen conflicting reports on whether each of these components helped protect cells from viruses," says James Stivers, Ph.D., a professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences. "By plotting how much of each are found in different types of cells, as well as the cells' response to HIV, we learned that both are needed to get the protective effect."

Researchers have long known that DNA's code is made up of four building blocks called nucleotides, commonly abbreviated A, T, G, and C. Before a cell divides, DNA-copying enzymes string these nucleotides together based on existing templates, so that each of the new cells gets its own copy of the genome. But because the T nucleotide, dTTP, is very similar to dUTP, a fifth nucleotide that doesn't belong in DNA, the copying enzyme sometimes mistakenly puts in a U where there should be a T.

To prevent this, says Stivers, most human cell types have an enzyme whose job is to break down dUTP, keeping its levels very low. Another quality control measure is the enzyme hUNG2, which snips stray Us out of newly copied DNA strands, leaving the resulting holes to be filled by a different repair enzyme. Certain immune cells called resting cells lack the first quality-control mechanism because, Stivers explain
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Contact: Shawna Williams
shawna@jhmi.edu
410-955-8236
Johns Hopkins Medicine
Source:Eurekalert  

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