Taming Mre11-Rad50 at Telomeres: Convergent Strategies for Chromosome-End Protection Across Evolution

Telomere biology is often framed as a uniquely eukaryotic problem, yet the challenges of maintaining DNA ends are shared by all organisms harboring linear DNA, including viral entities. Telomeres enable complete replication of chromosome ends while shielding the termini from DNA repair factors and innate immune surveillance systems that would otherwise recognize them as damaged or foreign DNA. A particular threat is posed by Mre11-Rad50, a nuclease complex conserved from bacteria to humans that specializes in the detection and processing of DNA ends. The solutions to these DNA end-related challenges that have emerged across the tree of life converge on a small number of recurring strategies. Here, we review how diverse biological systems, from bacteriophages to mammals, have solved the DNA end-related challenges, with a particular focus on recent advances in our understanding of end protection.