期刊
MOLECULAR CELL
卷 82, 期 18, 页码 3513-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2022.07.019
关键词
-
资金
- Deutsche Forschungsgemeinschaft [HO2489/11-1, CRC1054, 210592381]
- Gottfried-Wilhelm- Leibniz Prize
- Research Training Group [1721]
- International Max Planck Research School of Molecular and Cellular Life Sciences
- Boehringer Ingel- heim Fonds (BIF)
- [CRC1361]
This study reveals the mechanism of action of the Mre11-Rad50 complex in DNA repair. The results show that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage and processes internal DNA, DNA ends, and hairpins in a similar ATP-regulated conformational state.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据