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Enzyme corrects more than 1 million faults in DNA replication
Date:5/11/2012

Scientists from the Medical Research Council (MRC) Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh have discovered an enzyme that corrects the most common mistake in mammalian DNA.

The mistake is the inclusion of individual bits of RNA within the DNA sequence, which the researchers found occurs more than a million times in each cell as it divides. The findings, published in Cell, suggest the RNase H2 enzyme is central to an important DNA repair mechanism necessary to protect the human genome.

Each time a cell divides it must first make an identical copy of its entire genetic material, known as the genome. During this process, which is called DNA replication, the integrity of the genetic code is safeguarded by cellular 'proofreading' and error checking mechanisms.

But sometimes mistakes creep into the genetic code, which if not corrected could lead to genetic disease or cancer. Accidental incorporation of RNA is one such mistake. The individual building blocks of RNA (ribonucleotides) are very similar to those that make up DNA, however, they are much less stable and if they remain incorporated in DNA they cause harmful breaks in the double helix. Such breaks are common in cancer cells.

The researchers made the discovery while working on a rare childhood auto-immune disease known as Aicardi-Goutires syndrome, which is caused by mutations in the RNase H2 genes. It leads to inflammation of the brain soon after birth and can be fatal within the first few years of life.

To study this condition in more detail, the scientists knocked out one of the RNase H2 genes in mice. They found that without the enzyme, the developing mouse embryos accumulated more than 1,000,000 single embedded bits of RNA in the genome of every cell, resulting in instability of their DNA.

Dr Andrew Jackson from the MRC IGMM at the University of Edinburgh, who led the research, said:

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Contact: Hannah Isom
press.office@headoffice.mrc.ac.uk
44-207-395-2345
University of Edinburgh
Source:Eurekalert

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