7z03
From Proteopedia
Endonuclease state of the E. coli Mre11-Rad50 (SbcCD) head complex bound to ADP and extended dsDNA
Structural highlights
FunctionSBCC_ECOLI SbcCD cleaves DNA hairpin structures. These structures can inhibit DNA replication and are intermediates in certain DNA recombination reactions. The complex acts as a 3'->5' double strand exonuclease that can open hairpins. It also has a 5' single-strand endonuclease activity. Publication Abstract from PubMedDNA 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 physiologically critical endonuclease activity by the Mre11-Rad50 complex. Here, we report cryoelectron microscopy (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. Structural mechanism of endonucleolytic processing of blocked DNA ends and hairpins by Mre11-Rad50.,Gut F, Kashammer L, Lammens K, Bartho JD, Boggusch AM, van de Logt E, Kessler B, Hopfner KP Mol Cell. 2022 Sep 15;82(18):3513-3522.e6. doi: 10.1016/j.molcel.2022.07.019. , Epub 2022 Aug 19. PMID:35987200[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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