Nature Cell Biology study says Cdk5 protein is required to activate ATM before it can help neurons.
Researchers from Emory University have identified a biochemical switch required for nerve cells to respond to DNA damage. The ataxia telangiectasia mutated (ATM) gene, which encodes an enzyme that controls cells’ response to and repair of DNA damage, cannot activate itself directly.
Though ATM can be turned on experimentally by treating cells with chemicals that damage DNA, the gene must be activated by the Cdk5 protein before it will detect broken DNA and begin repairing it.
Cdk5 contributes to normal brain development, and aberrant Cdk5 activity is known to be involved in the death of neurons in several neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis.
Scientists were intrigued by reports that in these diseases, neurons that had stopped dividing appear to restart that process, copying their DNA before dying.
“Cdk5 has a complex character,” says Zixu Mao, M.D., Ph.D., an associate professor of pharmacology and neurology at Emory University School of Medicine.“It can be bad for neurons if its activity is either too high or too low.”
The same process, called mitotic catastrophe, occurs when neurons suffer DNA damage. Inhibiting either Cdk5 or ATM can reduce the number of neurons that suffer mitotic catastrophe after DNA damage.
The article appears in the advanced online version of Nature Cell Biology.
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