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 end binding / DNAリガーゼ / 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 / protein localization to site of double-strand break / DNA ligation / regulation of smooth muscle cell proliferation / V(D)J遺伝子再構成 / nuclear telomere cap complex / Cytosolic sensors of pathogen-associated DNA / double-strand break repair via classical nonhomologous end joining / クラススイッチ / regulation of epithelial cell proliferation / IRF3-mediated induction of type I IFN / telomere capping / 相同組換え / regulation of telomere maintenance / nucleotide-excision repair, DNA gap filling / double-strand break repair via alternative nonhomologous end joining / regulation of hematopoietic stem cell differentiation / U3 snoRNA binding / positive regulation of neurogenesis / cellular response to fatty acid / hematopoietic stem cell proliferation / protein localization to chromosome, telomeric region / cellular hyperosmotic salinity response / maturation of 5.8S rRNA / T cell lineage commitment / response to ionizing radiation / negative regulation of cGAS/STING signaling pathway / telomeric DNA binding / DNA biosynthetic process / cellular response to lithium ion / B cell lineage commitment / positive regulation of catalytic activity / 2-LTR circle formation / positive regulation of double-strand break repair via nonhomologous end joining / site of DNA damage / somatic stem cell population maintenance / ligase activity / 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 / chromosome organization / hematopoietic stem cell differentiation / positive regulation of protein kinase activity / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / enzyme activator activity / somitogenesis / SUMOylation of DNA damage response and repair proteins / DNA polymerase binding / condensed chromosome / positive regulation of telomerase activity / mitotic G1 DNA damage checkpoint signaling / positive regulation of telomere maintenance via telomerase / activation of innate immune response / DNA helicase activity / telomere maintenance / cyclin binding / 神経発生 / B cell differentiation / positive regulation of erythrocyte differentiation / negative regulation of protein phosphorylation / cellular response to leukemia inhibitory factor / central nervous system development / stem cell proliferation / positive regulation of translation / cellular response to ionizing radiation / small-subunit processome / デオキシリボ核酸 / response to gamma radiation / Nonhomologous End-Joining (NHEJ) / peptidyl-threonine phosphorylation / 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 / protein destabilization 類似検索 - 分子機能
Protein PAXX / PAXX, PAralog of XRCC4 and XLF, also called C9orf142 / 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 / XRCC4 ...Protein PAXX / PAXX, PAralog of XRCC4 and XLF, also called C9orf142 / 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 / 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 / PIK-related kinase, FAT / FAT domain / FATC 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
デオキシリボ核酸 / DNA (> 10) / X-ray repair cross-complementing protein 6 / X-ray repair cross-complementing protein 5 / DNA ligase 4 / DNA-dependent protein kinase catalytic subunit / XRCC4 / Protein PAXX / Non-homologous end-joining factor 1 類似検索 - 構成要素
ジャーナル: Sci Adv / 年: 2023 タイトル: PAXX binding to the NHEJ machinery explains functional redundancy with XLF. 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 / ...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 / 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.
A: DNA-dependent protein kinase catalytic subunit B: X-ray repair cross-complementing protein 6 C: X-ray repair cross-complementing protein 5 D: Protein PAXX G: DNA repair protein XRCC4 H: DNA repair protein XRCC4 I: DNA ligase 4 L: X-ray repair cross-complementing protein 5 M: Protein PAXX P: DNA repair protein XRCC4 Q: DNA repair protein XRCC4 R: DNA ligase 4 S: DNA-dependent protein kinase catalytic subunit T: X-ray repair cross-complementing protein 6 d: DNA (25-MER) e: DNA (27-MER) i: DNA (26-MER) j: DNA (5'-D(P*AP*AP*TP*AP*AP*TP*AP*GP*TP*TP*TP*TP*TP*AP*GP*TP*TP*TP*AP*TP*TP*GP*GP*G)-3') f: Non-homologous end-joining factor 1 m: Non-homologous end-joining factor 1