Rare genetic diseases associated with G-quadruplex-induced replication stress.

WHY IT MATTERS

Understanding which genes cause these G-quadruplex problems could help doctors diagnose patients with unexplained immunodeficiency, growth delays, or birth defects, and may eventually lead to targeted treatments for these currently untreatable conditions.

Scientists have discovered that certain rare genetic diseases are caused by mutations in genes that help cells copy their DNA. These genes normally produce proteins that untangle special twisted DNA structures called G-quadruplexes that get in the way during copying. When these proteins don't work properly, cells can't copy their DNA correctly, leading to problems like weak immune systems, slow growth, birth defects, and increased cancer risk.

Rare genetic diseases associated with G-quadruplex-induced replication stress. Abstract: DNA replication stress is incurred by endogenous or environmental challenges to replication fork progression that impede faithful genome duplication. Genomic G-quadruplexes (G4s) are DNA secondary structures that present a substantial barrier for passage of the replisome, and DNA synthesis past these structures requires dynamic remodeling by specialized helicases, translocases, and other G4-binding proteins to facilitate G4 resolution or bypass. Mutations in the genes encoding these auxiliary replication proteins are linked to hereditary disorders presenting with a range of clinical features, including immunodeficiency, growth restriction, congenital abnormalities, and cancer predisposition, demonstrating that these G4-metabolizing proteins also play broader roles in genome biology such as Authors: Herr et al. Journal: Communications biology MeSH: G-Quadruplexes, Humans, DNA Replication, Rare Diseases, DNA Helicases, Genomic Instability, Genetic Diseases, Inborn, Mutation, Animals