Saturday, March 10, 2007

The Effects of a Change in One Protein

The website 'Medical News Today' published an article titled 'Why some DNA repair fails - Mayo Clinic research' which covers a topic of interest within this blog. Quoting a section of the article:

"From bacteria to humans, cells have evolved sophisticated means of repairing DNA that gets damaged -- by a variety of causes -- ranging from environmental stresses to inherent copying errors. Repair is necessary to prevent accumulations of mutations that can cause disease. Repair is therefore a normal part of a day in the life of DNA. As cells grow and divide, mismatch repair pathways are responsible for identifying irregular growth patterns and repairing specific irregularities in DNA.

Wrong Place at the Wrong Time

Dr. McMurray's group studied a specific mismatch repair protein Msh2-Msh3 and found a paradox: Instead of helping repair DNA damage, under certain conditions, Msh2-Msh3 was actually harming the cell. Msh2-Msh3 did this when it arrived at the wrong place at the wrong time and bound to a specific portion of DNA (CAG-hairpin). This accident of binding at the CAG-hairpin altered the biochemical activity of Msh2-Msh3. This change in biochemical activity, in turn, promoted DNA expansion -- rather than repair -- and changed the function of Msh2-Msh3 from friend of DNA to foe by allowing damaged DNA to go unrepaired. Without DNA repair, mutations accumulate that lead to disease."


This illustrates a general principle common to life. Where a mechanism exists, having a specified function, a malfunction of that mechanism leads to an aberrancy which can induce diseases that are lethal to organisms or compromise their reproductive fitness. In this case the malfunction involves a specific protein whose altered behavoir changed its role from one of DNA repair to DNA expansion. A resulting increase in accumulating mutations can lead to disease.

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