Abstract
DNA double-strand breaks (DSBs) threaten genome stability and are linked to tumorigenesis in humans. Repair of DSBs requires the removal of attached proteins and hairpins through a poorly understood but phys-iologically critical endonuclease activity by the Mre11-Rad50 complex. Here, we report cryoelectron micro-scopy (cryo-EM) structures of the bacterial Mre11-Rad50 homolog SbcCD bound to a protein-blocked DNA end and a DNA hairpin. The structures reveal that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage and show how internal DNA, DNA ends, and hairpins are processed through a similar ATP-regulated conformational state. Furthermore, Mre11-Rad50 is loaded onto blocked DNA ends with Mre11 pointing away from the block, explaining the distinct biochemistries of 3'-> 5' exonucleolytic and endonucleolytic incision through the way Mre11-Rad50 interacts with diverse DNA ends. In summary, our results unify Mre11-Rad50's enigmatic nuclease diversity within a single structural framework and reveal how blocked DNA ends and hairpins are processed.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
Chemie und Pharmazie > Department Biochemie |
Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
ISSN: | 1097-2765 |
Sprache: | Englisch |
Dokumenten ID: | 111234 |
Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2024, 07:24 |
Letzte Änderungen: | 02. Apr. 2024, 07:24 |