- PDB-6wh2: Structure of the C-terminal BRCT domain of human XRCC1 -
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基本情報
登録情報
データベース: PDB / ID: 6wh2
タイトル
Structure of the C-terminal BRCT domain of human XRCC1
要素
X-ray repair cross complementing protein 1 variant
キーワード
DNA BINDING PROTEIN / DNA ligase complex / DNA repair
機能・相同性
機能・相同性情報
3' overhang single-stranded DNA endodeoxyribonuclease activity / oxidized DNA binding / positive regulation of DNA ligase activity / telomeric DNA-containing double minutes formation / ERCC4-ERCC1 complex / negative regulation of protection from non-homologous end joining at telomere / ADP-D-ribose modification-dependent protein binding / negative regulation of protein ADP-ribosylation / poly-ADP-D-ribose binding / positive regulation of single strand break repair ...3' overhang single-stranded DNA endodeoxyribonuclease activity / oxidized DNA binding / positive regulation of DNA ligase activity / telomeric DNA-containing double minutes formation / ERCC4-ERCC1 complex / negative regulation of protection from non-homologous end joining at telomere / ADP-D-ribose modification-dependent protein binding / negative regulation of protein ADP-ribosylation / poly-ADP-D-ribose binding / positive regulation of single strand break repair / voluntary musculoskeletal movement / cerebellum morphogenesis / single strand break repair / replication-born double-strand break repair via sister chromatid exchange / HDR through MMEJ (alt-NHEJ) / response to hydroperoxide / Resolution of AP sites via the single-nucleotide replacement pathway / APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway / site of DNA damage / : / Gap-filling DNA repair synthesis and ligation in GG-NER / hippocampus development / base-excision repair / double-strand break repair via nonhomologous end joining / Gap-filling DNA repair synthesis and ligation in TC-NER / chromosome, telomeric region / damaged DNA binding / response to hypoxia / response to xenobiotic stimulus / chromatin / nucleolus / enzyme binding / nucleoplasm / nucleus 類似検索 - 分子機能
DNA-repair protein Xrcc1, N-terminal / XRCC1, first (central) BRCT domain / XRCC1 N terminal domain / BRCT domain, a BRCA1 C-terminus domain / BRCA1 C Terminus (BRCT) domain / breast cancer carboxy-terminal domain / BRCT domain profile. / BRCT domain / BRCT domain superfamily / Galactose-binding-like domain superfamily 類似検索 - ドメイン・相同性
DNA repair protein XRCC1 / X-ray repair cross complementing protein 1 variant 類似検索 - 構成要素
ジャーナル: Nucleic Acids Res / 年: 2021 タイトル: An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex. 著者: Michal Hammel / Ishtiaque Rashid / Aleksandr Sverzhinsky / Yasin Pourfarjam / Miaw-Sheue Tsai / Tom Ellenberger / John M Pascal / In-Kwon Kim / John A Tainer / Alan E Tomkinson / 要旨: The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined ...The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle light scattering (SEC-SAXS-MALS), we determined that the XL is more compact than either XRCC1 or LigIIIα, both of which form transient homodimers and are highly disordered. The reduced disorder and flexibility allowed us to build models of XL particles visualized by negative stain electron microscopy that predict close spatial organization between the LigIIIα catalytic core and both BRCT domains of XRCC1. Together our results identify an atypical BRCT-BRCT interaction as the stable nucleating core of the XL that links the flexible nick sensing and catalytic domains of LigIIIα to other protein partners of the flexible XRCC1 scaffold.