Researchers working at the University of Bradford, UK, have identified a DNA protein ‘switch’ that may assist in the treatment of cancer and dementia.
The scientists have identified a mechanism that regulates the creation of R-loops. These are part DNA and they regulate the production of proteins in the human body. The R-loops ‘brittle’ and prone to breaking. In terms of importance, if there are too many R-loops, this can lead to cell death and where there are insufficient loops, this causes disruption to protein production. Importantly, R loops are an important source of replication stress and genome instability, which are hallmarks of cancer.
The researchers have determined the mechanism by which R-loops are regulated DNA. R- loops can be are visualised by electron microscopy and reveal intron regions of DNA by creating unbound loops at these regions.
According to the lead researcher Professor El-Khamisy, in a stamen provided to Digital Journal, not only is the research of importance for understanding how R-loops are regulated in human cells, but the study is also significant it may mean “we can design drugs to manipulate the process in the way we want. We are getting one step closer to finding drugs that can modify the progression of some diseases including cancer, dementia and conditions which affect co-ordination.” These various illnesses appear to relate to the disruption of R-loops.
The study discovered three proteins which regulate R-loops. These are named senataxin, USP11 and KEAP1. The three proteins are located in a ‘pathway’ and they work together as a team in order to regulate the levels of R-loops and take them to the optimal level for making proteins. This regulation is driven by a small molecule called ubiquitin.
Additionally, the findings show how human cells fine-tune R-loops and also how they deal with a loss of a protein – an event commonly found in cancer.
It is possible, from the research, to manufacture medicines that could increase R-loops, which would be useful in killing cells (something that would aid in cancer treatment). From a different perspective, inf a drug could be developed to reduce the level of R-loops, this could be beneficial for dementia and some genetic conditions that affect muscle co-ordination.
The research output appears in the journal Nature Communications.
