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-Structure paper
タイトル | Autophosphorylation transforms DNA-PK from protecting to processing DNA ends. |
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ジャーナル・号・ページ | Mol Cell, Vol. 82, Issue 1, Page 177-189.e4, Year 2022 |
掲載日 | 2022年1月6日 |
著者 | Lan Liu / Xuemin Chen / Jun Li / Huaibin Wang / Christopher J Buehl / Noah J Goff / Katheryn Meek / Wei Yang / Martin Gellert / |
PubMed 要旨 | The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends ...The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events. |
リンク | Mol Cell / PubMed:34936881 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.7 - 4.4 Å |
構造データ | EMDB-25110: EMDB-25111: EMDB-25112: EMDB-25113, PDB-7sgl: EMDB-25114: EMDB-25115: EMDB-25439, PDB-7su3: EMDB-25440, PDB-7sud: |
化合物 | ChemComp-MG: ChemComp-ATP: ChemComp-IHP: ChemComp-ZN: |
由来 |
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キーワード | DNA BINDING PROTEIN/DNA / endonuclease / Kinase / complex / DNA BINDING PROTEIN / TRANSFERASE / DNA BINDING PROTEIN-DNA complex / NHEJ / DNA-PK / DNA repair |