The gray boundaries of aberrant shortening of the cellular timekeepers’ edges

• Published in: EMBO molecular medicine 2024-08, Vol.16 (10), p.2276-2278
• Main Authors: Guenechea, Guillermo, Meza, Nestor W
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; EMBO16; Molecular Medicine; News & Views; news-and-views; Views
• ISSN: 1757-4684; 1757-4676; 1757-4684
• DOI: 10.1038/s44321-024-00122-1

Telomeres are supramolecular structures that allow the DNA strand to fold back on itself and protect the linear chromosome end from being sensed as a double-strand DNA break. Telomeric conservation relies on mechanisms that replace terminal DNA sequences, and ensuring structural integrity. Telomere biology disorders (TBDs) are a heterogeneous group of low-prevalence pathologies defined by germline mutations in genes involved in telomere maintenance mechanisms (TMMs). TBDs manifest across a broad clinical spectrum, often with substantial phenotypic and genetic overlap among clinical entities. In this issue of EMBO Molecular Medicine , Tummala and collaborators present clinical and biological data from DC/DCL patients, that enhances the understanding of the natural history of these diseases. In addition, the description of novel TBD-associated genetic variants in POT1 and ZCCHC8 and of the new POLA1 gene advances the understanding of the functional network of genes involved in TBD and highlights new pathogenic mechanisms. N. Meza and G. Guenechea discuss novel genetic variants identified in telomere biology disorder dyskeratosis congenita (DC) and DC-like patients, as reported by Tummala and colleagues in this issue of EMBO Mol Med .