The Mre11–Rad50-(Nbs1/Xrs2) complex is an evolutionarily conserved factor for the repair of DNA double-strand breaks and other DNA termini in all kingdoms of life. It is an intricate DNA associated molecular machine that cuts, among other functions, a large variety of free and obstructed DNA termini for DNA repair by end joining or homologous recombination, yet leaves undamaged DNA intact. Recent years have brought progress in both the structural and functional analyses of Mre11–Rad50 orthologs, revealing mechanisms of DNA end recognition, endo/exonuclease activities, nuclease regulation and DNA scaffolding. Here, I review our current understanding and recent progress on the functional architecture Mre11–Rad50 and how this chromosome associated coiled-coil ABC ATPase acts as DNA topology specific endo-/exonuclease.
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The cover of this edition of Biochemical Society Transactions features a super-resolution image of mouse heart mitochondria. Shammas, Huang and Narendra discuss the present understanding of neurodegeneration and myopathy caused by mutations in the mitochondrial proteins CHCHD2 and CHCHD10, and putting forth potential therapeutic strategies to combat these diseases in ‘CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy’ on pp 797-809.
Mre11–Rad50: the DNA end game Available to Purchase
Karl-Peter Hopfner; Mre11–Rad50: the DNA end game. Biochem Soc Trans 26 April 2023; 51 (2): 527–538. doi: https://doi.org/10.1042/BST20220754
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