Genetic determinants of micronucleus formation


More than one hundred key genes linked to DNA damage have been uncovered through systematic screening of nearly 1,000 genetically modified mouse lines, in a new study published in Nature.

The work provides insights into cancer progression and neurodegenerative diseases as well as a potential therapeutic avenue in the form of a protein inhibitor.

The genome contains all the genes and genetic material within an organism's cells. When the genome is stable, cells can accurately replicate and divide, passing on correct genetic information to the next generation of cells. Despite its significance, little is understood about the genetic factors governing genome stability, protection, repair, and the prevention of DNA damage1.

In this new study, researchers set out to better understand the biology of cellular health and identify genes key to maintaining genome stability.

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

The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Mice lacking this gene mirrored characteristics akin to human patients with cohesinopathy disorders, further emphasising the relevance of this research to human health.

Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT1. This offers a highly promising avenue for the development of new therapies.

The findings help shed light on genetic factors influencing the health of human genomes over a lifespan and disease development.

https://www.nature.com/articles/s41586-023-07009-0

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fgenetic-determinants-of_3&filter=22

Rating

Unrated
Rating: