How stress causes DNA damage

Working closely with a team of researchers from Duke University, scientists from the Florida campus of The Scripps Research Institute have helped identify a molecular pathway that plays a key role in stress-related damage to the genome, the entirety of an organism’s hereditary information.

The new findings could explain the development of certain human disorders, and also offer a potential model for prevention and therapy.

While the human mind and body are built to respond to stress — the well-known “fight or flight” response, which lasts only a few minutes and raises heart rate and blood glucose levels — the response itself can cause significant damage if maintained over long periods of time.

When stress becomes chronic, this natural response can lead to a number of disease-related symptoms, including peptic ulcers and cardiovascular disorders. To make matters worse, evidence indicates that chronic stress eventually leads to DNA damage, which in turn can result in various neuropsychiatric conditions, miscarriages, cancer, and even aging itself.

How stress damages DNA

Until the new study, however, exactly how chronic stress wreaks havoc on DNA was basically unknown.  “Our results provide a possible mechanistic basis for several recent reports suggesting that significant risk reductions for diseases such as prostate cancer, lung adenocarcinoma, and Alzheimer’s disease may be associated with blockade of this particular stress-response pathway by beta blockers,”  said Robert J. Lefkowitz, a Duke University professor of medicine who led the study.

“Although there are most likely numerous pathways involved in the onset of stress-related diseases, our results raise the possibility that such therapies might reduce some of the deleterious DNA-damaging consequences of long-term stress in humans.”

The newly uncovered mechanism involves β-arrestin-1proteins, β2-adrenoreceptors (β2ARs), and the catecholamines, the classic fight-or-flight hormones released during times of stress — adrenaline, noradrenaline, and dopamine. Arrestin proteins are involved in modifying the cell’s response to neurotransmitters, hormones, and sensory signals; adrenoceptors respond to the catecholamines noradrenaline and adrenaline.

Under stress, the hormone adrenaline stimulates β2ARs expressed throughout the body, including sex cells and embryos. Through a series of complex chemical reactions, the activated receptors recruit β-arrestin-1, creating a signaling pathway that leads to catecholamine-induced degradation of the tumor suppressor protein p53, sometimes described as “the guardian of the genome.”

The new findings also suggest that this degradation of p53 leads to chromosome rearrangement and a build-up of DNA damage both in normal and sex cells. These types of abnormalities are the primary cause of miscarriages, congenital defects, and mental retardation, the study noted.

Source: http://goo.gl/jpIlm

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