登録情報 データベース : EMDB / ID : EMD-23510 構造の表示 ダウンロードとリンクタイトル NHEJ Long-range synaptic complex マップデータPre-synaptic complex 詳細 試料複合体 : Long-range synaptic Complex of NHEJタンパク質・ペプチド : X-ray repair cross-complementing protein 6タンパク質・ペプチド : X-ray repair cross-complementing protein 5タンパク質・ペプチド : DNA-dependent protein kinase catalytic subunitタンパク質・ペプチド : Unknown peptideDNA : DNA (31-MER)DNA : DNA (30-MER)タンパク質・ペプチド : DNA repair protein XRCC4タンパク質・ペプチド : Non-homologous end-joining factor 1タンパク質・ペプチド : DNA ligase 4 残り5件を表示 表示を減らすリガンド : ADENOSINE-5'-DIPHOSPHATE 詳細 キーワード NHEJ / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
DNA ligation involved in DNA recombination / FHA domain binding / positive regulation of chromosome organization / positive regulation of ligase activity / DNA ligase IV complex / DNA ligation involved in DNA repair / DNA ligase activity / Ku70:Ku80 complex / DN2 thymocyte differentiation / negative regulation of t-circle formation ... DNA ligation involved in DNA recombination / FHA domain binding / positive regulation of chromosome organization / positive regulation of ligase activity / DNA ligase IV complex / DNA ligation involved in DNA repair / DNA ligase activity / Ku70:Ku80 complex / DN2 thymocyte differentiation / negative regulation of t-circle formation / positive regulation of platelet formation / DNA ligase (ATP) / DNA end binding / T cell receptor V(D)J recombination / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA ligase (ATP) activity / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / DNA-dependent protein kinase complex / immature B cell differentiation / DNA-dependent protein kinase-DNA ligase 4 complex / single strand break repair / cellular response to X-ray / immunoglobulin V(D)J recombination / nonhomologous end joining complex / DNA ligation / regulation of smooth muscle cell proliferation / V(D)J recombination / nuclear telomere cap complex / Cytosolic sensors of pathogen-associated DNA / double-strand break repair via classical nonhomologous end joining / isotype switching / protein localization to site of double-strand break / regulation of epithelial cell proliferation / IRF3-mediated induction of type I IFN / telomere capping / recombinational repair / regulation of telomere maintenance / regulation of hematopoietic stem cell differentiation / U3 snoRNA binding / positive regulation of neurogenesis / cellular response to fatty acid / nucleotide-excision repair, DNA gap filling / hematopoietic stem cell proliferation / protein localization to chromosome, telomeric region / cellular hyperosmotic salinity response / T cell lineage commitment / response to ionizing radiation / negative regulation of cGAS/STING signaling pathway / DNA biosynthetic process / cellular response to lithium ion / telomeric DNA binding / maturation of 5.8S rRNA / double-strand break repair via alternative nonhomologous end joining / positive regulation of catalytic activity / B cell lineage commitment / 2-LTR circle formation / positive regulation of double-strand break repair via nonhomologous end joining / ligase activity / site of DNA damage / somatic stem cell population maintenance / 付加脱離酵素(リアーゼ); 炭素-酸素リアーゼ類; その他の炭素-酸素リアーゼ / T cell differentiation / response to X-ray / 5'-deoxyribose-5-phosphate lyase activity / hematopoietic stem cell differentiation / chromosome organization / positive regulation of protein kinase activity / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / somitogenesis / SUMOylation of DNA damage response and repair proteins / DNA polymerase binding / condensed chromosome / DNA helicase activity / : / enzyme activator activity / mitotic G1 DNA damage checkpoint signaling / positive regulation of telomere maintenance via telomerase / activation of innate immune response / telomere maintenance / cyclin binding / B cell differentiation / neurogenesis / positive regulation of erythrocyte differentiation / negative regulation of protein phosphorylation / stem cell proliferation / cellular response to leukemia inhibitory factor / central nervous system development / positive regulation of translation / cellular response to ionizing radiation / response to gamma radiation / protein-DNA complex / small-subunit processome / Nonhomologous End-Joining (NHEJ) / 加水分解酵素; 酸無水物に作用; 酸無水物に作用・細胞または細胞小器官の運動に関与 / peptidyl-threonine phosphorylation / protein destabilization 類似検索 - 分子機能 XLF, N-terminal / XLF N-terminal domain / DNA ligase IV domain / DNA ligase IV / DNA ligase 4 / DNA Ligase 4, adenylation domain / XRCC4, N-terminal domain superfamily / DNA repair protein XRCC4 / XRCC4 N-terminal domain / XRCC4-like, N-terminal domain superfamily ... XLF, N-terminal / XLF N-terminal domain / DNA ligase IV domain / DNA ligase IV / DNA ligase 4 / DNA Ligase 4, adenylation domain / XRCC4, N-terminal domain superfamily / DNA repair protein XRCC4 / XRCC4 N-terminal domain / XRCC4-like, N-terminal domain superfamily / Ku70, bridge and pillars domain superfamily / : / Ku70 / Ku, C-terminal / Ku, C-terminal domain superfamily / Ku C terminal domain like / Ku80 / Ku70/Ku80 C-terminal arm / Ku70/Ku80, N-terminal alpha/beta / Ku70/Ku80 beta-barrel domain / Ku70/Ku80 C-terminal arm / Ku70/Ku80 N-terminal alpha/beta domain / Ku70 and Ku80 are 70kDa and 80kDa subunits of the Lupus Ku autoantigen / Ku70/Ku80 beta-barrel domain / DNA ligase, ATP-dependent / DNA ligase, ATP-dependent, N-terminal / DNA ligase, ATP-dependent, N-terminal domain superfamily / DNA ligase N terminus / DNA-dependent protein kinase catalytic subunit, CC3 / SPOC-like, C-terminal domain superfamily / DNA-dependent protein kinase catalytic subunit, catalytic domain / DNA-dependent protein kinase catalytic subunit, CC5 / DNA-dependent protein kinase catalytic subunit, CC1/2 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC3 / DNA-PKcs, CC5 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC1/2 / NUC194 / ATP-dependent DNA ligase signature 2. / ATP-dependent DNA ligase AMP-binding site. / DNA ligase, ATP-dependent, C-terminal / ATP dependent DNA ligase C terminal region / DNA ligase, ATP-dependent, conserved site / ATP-dependent DNA ligase family profile. / SAP domain superfamily / DNA ligase, ATP-dependent, central / ATP dependent DNA ligase domain / DNA repair protein XRCC4-like, C-terminal / SAP domain / SAP motif profile. / Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation / SAP domain / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / BRCA1 C Terminus (BRCT) domain / Phosphatidylinositol 3- and 4-kinases signature 1. / breast cancer carboxy-terminal domain / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / von Willebrand factor (vWF) type A domain / von Willebrand factor, type A / BRCT domain profile. / BRCT domain / BRCT domain superfamily / von Willebrand factor A-like domain superfamily / Armadillo-like helical / Armadillo-type fold / Nucleic acid-binding, OB-fold / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 X-ray repair cross-complementing protein 6 / X-ray repair cross-complementing protein 5 / DNA ligase 4 / DNA-dependent protein kinase catalytic subunit / DNA repair protein XRCC4 / Non-homologous end-joining factor 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.6 Å 詳細 データ登録者He Y / Chen S 資金援助 米国, 6件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01GM135651 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) 5T32GM008382 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) U24GM129547 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) P01CA092584 米国 American Cancer Society IRG-15-173-21 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01GM047251 米国
引用ジャーナル : Nature / 年 : 2021タイトル : Structural basis of long-range to short-range synaptic transition in NHEJ.著者 : Siyu Chen / Linda Lee / Tasmin Naila / Susan Fishbain / Annie Wang / Alan E Tomkinson / Susan P Lees-Miller / Yuan He / 要旨 : DNA double-strand breaks (DSBs) are a highly cytotoxic form of DNA damage and the incorrect repair of DSBs is linked to carcinogenesis. The conserved error-prone non-homologous end joining (NHEJ) ... DNA double-strand breaks (DSBs) are a highly cytotoxic form of DNA damage and the incorrect repair of DSBs is linked to carcinogenesis. The conserved error-prone non-homologous end joining (NHEJ) pathway has a key role in determining the effects of DSB-inducing agents that are used to treat cancer as well as the generation of the diversity in antibodies and T cell receptors. Here we applied single-particle cryo-electron microscopy to visualize two key DNA-protein complexes that are formed by human NHEJ factors. The Ku70/80 heterodimer (Ku), the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), DNA ligase IV (LigIV), XRCC4 and XLF form a long-range synaptic complex, in which the DNA ends are held approximately 115 Å apart. Two DNA end-bound subcomplexes comprising Ku and DNA-PKcs are linked by interactions between the DNA-PKcs subunits and a scaffold comprising LigIV, XRCC4, XLF, XRCC4 and LigIV. The relative orientation of the DNA-PKcs molecules suggests a mechanism for autophosphorylation in trans, which leads to the dissociation of DNA-PKcs and the transition into the short-range synaptic complex. Within this complex, the Ku-bound DNA ends are aligned for processing and ligation by the XLF-anchored scaffold, and a single catalytic domain of LigIV is stably associated with a nick between the two Ku molecules, which suggests that the joining of both strands of a DSB involves both LigIV molecules. 履歴 登録 2021年2月18日 - ヘッダ(付随情報) 公開 2021年4月14日 - マップ公開 2021年4月14日 - 更新 2024年3月6日 - 現状 2024年3月6日 処理サイト : RCSB / 状態 : 公開
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