Integrating structural dynamics and functional diversity of archaeal Mre11 proteins in DNA repair: A review.

DNA double-stranded breaks (DSBs) are highly cytotoxic lesions requiring precise repair to maintain genomic stability. Mre11 protein, which is universally conserved across all domains of life and viruses, partners with Rad50 to drive DSB repair via homologous recombination. While Mre11's dual enzymatic activities (3' → 5' exonuclease and ssDNA endonuclease) and conserved tripartite architecture (nuclease domain, capping domain, and Rad50-binding motif) are well-documented, archaeal homologs exhibit both functional conservation and divergence. Six archaeal Mre11 proteins reveal distinct function and repair mechanisms, which are likely shaped by extreme environmental pressures. This review summarizes recent advances on archaeal Mre11 proteins, focusing on difference between archaeal species and between these proteins from archaea and other organisms to better understand their structure-function relationship. Future research should address how archaeal Mre11 proteins balance conservation with lineage-specific adaptation, offering novel tools and insights for DNA repair biology.