The line of communication between two critical parts of a human cell could be the key to cell survival under stress – a finding that could deepen our understanding of various cancers, according to new research from the University of Surrey.
Research has found that when a cell is under stress, the presence of a critical enzyme, known as AAG, is important in ensuring that the various stress response pathways communicate properly.
Our cells are constantly under stress, and they respond to it by activating pathways to repair the damage. It’s the body’s way of calling 999 and dealing with emergencies. These stress responses are coordinated from distinct parts of the cell: the nucleus and the endoplasmic reticulum (ER).
We found that cells use an enzyme called AAG (Alkyladenine DNA Glycosylase) not only to repair DNA damage, but also to trigger stress responses that normally begin in the ER. We also found that the DNA repair activity of AAG was not required to activate this ER stress response, the presence of the protein, even if defective, was sufficient.”
Dr Lisiane Meira, Lecturer in DNA Damage and Ageing, Department of Clinical and Experimental Medicine (DCEM), University of Surrey
The researchers believe that this new nucleus-ER communication line is critical for cellular responses to alkylating agents, a class of drugs commonly used in cancer chemotherapy and found in environmental pollutants, such as cigarette smoke and tobacco products. fuel burning.
In the study, the researchers created cells that lack AAG and reintroduced the enzyme to study how the cell functions, particularly when alkylating agents damage it.
Dr. Meira continues:
“What is exciting about this project are its pharmacological possibilities – it could offer a step change in the way we view and treat certain cancers. Our team will now dig deeper into the mechanisms surrounding AAG and ER stress responses. This involves movement of proteins, or are other proteins in unknown cellular locations also involved in the process?
The research, which was published by the Proceedings of the US National Academy of Sciences (PNAS), was carried out in collaboration with St. George’s University of London in the UK and research groups in Brazil. , in Canada and the United States.
Milan, L., et al. (2022) A DNA repair-independent role for alkyladenine DNA glycosylase in the alkylation-induced unfolded protein response. PNAS. doi.org/10.1073/pnas.2111404119.