This study provides an understanding into the progression of cancer and neurodegenerative illnesses, as well as a potential therapeutic approach in the form of a protein inhibitor.
The genome encompasses all the genes and genetic material in an organism’s cells. When the genome is stable, cells can precisely replicate and divide, passing on the correct genetic information to the subsequent generation of cells. Despite its significance, little is known about the genetic factors that govern genome stability, protection, repair, and prevention of genome harm.
In this novel study, researchers from the Wellcome Sanger Institute and their colleagues from the UK Dementia Research Institute at the University of Cambridge set out to gain a better insight into the biology of cellular health and identify genes crucial for upholding genome stability.
Using a set of genetically modified mouse lines, the team uncovered 145 genes that play a crucial role in increasing or decreasing the development of abnormal micronuclei structures. These structures indicate genomic instability and DNA harm and are common characteristics of aging and diseases.
The most notable increase in genomic instability was observed when scientists disrupted the DSCC1 gene, elevating the development of abnormal micronuclei by five times. Mice lacking this gene exhibited traits similar to human patients with cohesinopathies, further highlighting the significance of this research for human health.
By employing CRISPR screening, researchers demonstrated that the impact induced by the loss of DSCC1 could be partially reversed by suppressing the SIRT1 protein. This reveals promising prospects for the evolution of new treatment methods.
The obtained data also illuminated the genetic factors influencing human genome health throughout life and the onset of illnesses.
Professor Gabriel Balmus, the senior author of the study at the UK Dementia Research Institute at the University of Cambridge, who formerly worked at the Wellcome Sanger Institute, commented, “Persisted research on genomic instability is crucial for formulating personalized treatment methods that eradicate the underlying genetic causes, with the objective of enhancing outcomes and overall quality of life for individuals with diverse conditions.”
“Our study emphasizes the potential of SIRT inhibitors as a therapeutic pathway for cohesinopathies and other genomic disorders. This implies that early intervention, particularly targeting SIRT1, may help alleviate biological changes associated with genomic instability before they advance.”
Dr. David Adams, the lead author of the study at the Wellcome Sanger Institute, remarked, “Genome stability is pivotal to cell health, influencing an array of illnesses from cancer to neurodegeneration, but it is a reasonably unexplored area of research.”
“This research, which lasted 15 years, is an illustration of what can be gleaned from large-scale, impartial genetic screening. The 145 identified genes, particularly those linked to human diseases, present encouraging targets for the development of new treatments for illnesses caused by genome instability, such as cancer and developmental disorders of the nervous system.”
Source: med2.ru