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Identify the molecular mechanisms that lead to DNA damage following a stress response.

Mice were infused with an analogue of the stress hormone adrenaline – isoproterenol, to create a model of chronic stress. These mice as well as a number of cell lines were used to investigate the effect isoproterenol on biological pathways involved in the stress response and their impact on DNA damage.

Chronically stressed mice and cell lines were shown to have DNA damage and an accumulation of chromosomal abnormalities. The levels of p53 - which is a protein involved in maintaining the integrity of the genome - are low in these mice. Biological pathways involving the β-arrestin-1 proteins, β2-adrenoreceptors (β2ARs), and catecholamines are involved in the mechanism leading to p53 degradation and subsequently DNA damage.

The β2-adrenoreceptor and signaling via the β-arrestin pathway regulate p53 degradation thus leading to the accumulation of DNA damage in both somatic and germline cells. This provides a mechanism by which chronic stress can lead to DNA damage.

It is widely acknowledged that chronic stress can lead to a number of adverse health outcomes and their impact on DNA damage has already been demonstrated. This study may eventually lead to the identification of potential therapies by identifying a pathway leading to DNA damage. However, as the authors note, this study has identified one mechanism of DNA damage and there may be others to uncover.