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-Structure paper
タイトル | PAXX binding to the NHEJ machinery explains functional redundancy with XLF. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 22, Page eadg2834, Year 2023 |
掲載日 | 2023年6月2日 |
著者 | Murielle Seif-El-Dahan / Antonia Kefala-Stavridi / Philippe Frit / Steven W Hardwick / Dima Y Chirgadze / Taiana Maia De Oliviera / Jessica Andreani / Sébastien Britton / Nadia Barboule / Madeleine Bossaert / Arun Prasad Pandurangan / Katheryn Meek / Tom L Blundell / Virginie Ropars / Patrick Calsou / Jean-Baptiste Charbonnier / Amanda K Chaplin / |
PubMed 要旨 | Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX ...Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in cells. |
リンク | Sci Adv / PubMed:37256950 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.68 - 5.33 Å |
構造データ | EMDB-14995, PDB-7zwa: EMDB-15022, PDB-7zyg: EMDB-16044, PDB-8bh3: EMDB-16070, PDB-8bhv: EMDB-16074, PDB-8bhy: PDB-8asc: |
化合物 | ChemComp-PO4: ChemComp-SO4: ChemComp-HOH: |
由来 |
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キーワード | DNA BINDING PROTEIN / NHEJ / Ku70 / Ku80 / DNA damage / PAXX / XLF / DNA repair / DNA-PK / DNA-PKcs |