Saturday, September 23, 2006

DNA Repair and the Enzyme OGG1

A HUM-MOLGEN article 'DNA Repair Enzyme Caught In The Act' reveals another cellular mechanism that helps to maintain genomic integrity. The italicized article is interspersed with my comments.

In the 31 March 2005 issue of Nature (Vol. 434, No. 7033, pp 612-618), researchers report the chemical structure of an enzyme vital for repairing routine damage to our DNA that is caused by oxidative damage. Their snap-shot of the protein captures it in the act of testing DNA for errors.

When oxidants attack DNA they can subtly alter the molecular building block guanine (G), creating a variation called 8-oxoguanine that can cause permanent mutations. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) recognizes and repairs 8-oxoguanine, and mutations in it have been linked to lung and possibly kidney cancer.

Note that the cause of the mutations is traced to effects of normal cellular activities. Normal cellular activities and environmental factors occasion the need for mechanisms that remedy damage to DNA and the effects of inevitable errors. Remedial functions are not optional. They are needed to maintain genomic function.

By determining the X-ray structure of human OGG1 bound to undamaged DNA, Gregory Verdine and his colleagues reveal how the enzyme efficiently scans for abnormal guanine residues embedded in a vast expanse of normal DNA, and how it removes them from the DNA helix without damaging normal bases.

The function specificity is clear but a precursor function of a homologous protein candidate is not.



At 8:19 AM, Anonymous Doug said...

Fine-tuning of the cosmos eat your heart out. Factors upon factors that are needed just to maintain the integrity of DNA from the products of normal cellular function.
How many separate processes and enzymes are utilized to safe-guard against the degradation of genomic information?

At 8:39 AM, Blogger William Bradford said...

Hi Doug. We are still finding new coping mechanisms as time goes on and learning more about those already known. Interestingly some of them have multiple enzymes yet appear to be highly conserved being found throughout the cellular world. This would be necessary to counter the effects of universal environmental causes of genomic decay and copying errors by cellular mechanisms. How a cell could survive in the absence of such mechanisms is not apparent. Nor is their evolution through selection. Of course wearing blinders is an option for those uncomfortable with the implications.


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