Key genes linked to DNA damage and human disease uncovered

This work provides insight into cancer progression and neurodegenerative diseases, as well as potential therapeutic pathways in the form of protein inhibitors.

The genome contains all the genes and genetic material contained within the cells of an organism. When the genome is stable, cells can replicate and divide correctly, passing on the correct genetic information to the next generation of cells. Despite its importance, little is understood about the genetic factors that control genome stability, protection, repair, and prevention of DNA damage.¹.

In this new study, researchers from the Wellcome Sanger Institute, and their colleagues at the UK Dementia Research Institute at the University of Cambridge, keyed genes to better understand the biology of cellular health and maintain genome stability. pointed out.

Using a set of genetically modified mouse lines, the team identified 145 genes that play a key role in increasing or decreasing the formation of abnormal micronuclei structures.². These structures indicate genomic instability and DNA damage, and are common symptoms of aging and diseases.

The most dramatic increase in genomic instability was observed when the researchers knocked out the gene. DSCC 1, a fivefold increase in the formation of abnormal micronuclei. The expression characteristics of this gene in mice are similar to those of human patients with cohesinopathy.³Further emphasizing the relevance of this research to human health.

Using CRISPR screening, the researchers demonstrated this effect. DSCC 1 The damage can be partially reversed by blocking the protein SIRT1.⁴. This provides a very promising opportunity for the development of new treatments.

The findings help shed light on genetic factors influencing the health of the human genome during life and disease development.

Professor Gabriel Balmes, senior author of the study at the UK’s Dementia Research Institute at the University of Cambridge, formerly at the Wellcome-Singer Institute, said: “Continued research into genomic instability is vital to developing treatments that target genetic disorders. suitable for addressing the causes. Aiming to improve outcomes and overall quality of life for individuals with a variety of conditions. Our study highlights the potential of SIRT inhibitors as a therapeutic pathway for cohesinopathies and other genomic disorders. . Biological changes linked to genomic instability before development.”

Dr. David Adams, first author of the study at the Wellcome Sanger Institute, said: “Genomic stability is central to the health of cells, affecting a spectrum of diseases from cancer to neurodegeneration, yet this research has been a relatively under-researched field. The work, 15 years in the making, exemplifies what can be learned from large-scale, unbiased genetic screening. 145 identified genes, particularly those associated with human disease. are, offer promising targets for developing new therapies for diseases driven by genome instability, such as cancer and neurodevelopmental disorders.”

Notice:

1. Various sources of damage to the genome may include radiation, chemical exposure, and errors during DNA replication or repair processes.
2. Micronuclei are small abnormal structures, often called “mutation factories,” that contain genetic material in the wrong place, where it should be in the cell’s nucleus. Their presence indicates an increased risk of diseases such as cancer and developmental disorders.
3. Cohesinopathy disorders are a group of genetic conditions that result from dysfunctional cohesin protein, which is essential for proper chromosome organization and segregation during cell division. It can lead to developmental abnormalities, intellectual disability, distinctive facial features and growth retardation.
4. When the SIRT1 protein was suppressed, DNA damage was reduced and they could rescue its negative effects. DSCC 1 Damage associated with syncope. This process was by restoring chemical levels of a protein called SMC3.