- EMDB-50294: Structure of Pol II-TC-NER-STK19 complex, focused on Pol II-ELOF1 -
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基本情報
登録情報
データベース: EMDB / ID: EMD-50294
タイトル
Structure of Pol II-TC-NER-STK19 complex, focused on Pol II-ELOF1
マップデータ
sharpened map (deepEMhancer)
試料
複合体: Ternary complex of Pol II-TC-NER-STK19, focused on Pol II-ELOF1
タンパク質・ペプチド: x 14種
DNA: x 2種
RNA: x 1種
キーワード
Transcription-coupled DNA repair / TRANSCRIPTION
機能・相同性
機能・相同性情報
RNA polymerase inhibitor activity / Formation of RNA Pol II elongation complex / Formation of the Early Elongation Complex / Transcriptional regulation by small RNAs / RNA Polymerase II Pre-transcription Events / TP53 Regulates Transcription of DNA Repair Genes / FGFR2 alternative splicing / RNA polymerase II transcribes snRNA genes / mRNA Capping / mRNA Splicing - Minor Pathway ...RNA polymerase inhibitor activity / Formation of RNA Pol II elongation complex / Formation of the Early Elongation Complex / Transcriptional regulation by small RNAs / RNA Polymerase II Pre-transcription Events / TP53 Regulates Transcription of DNA Repair Genes / FGFR2 alternative splicing / RNA polymerase II transcribes snRNA genes / mRNA Capping / mRNA Splicing - Minor Pathway / Processing of Capped Intron-Containing Pre-mRNA / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Elongation / RNA Polymerase II Transcription Initiation And Promoter Clearance / RNA Pol II CTD phosphorylation and interaction with CE / Estrogen-dependent gene expression / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / mRNA Splicing - Major Pathway / chromatin-protein adaptor activity / nuclear lumen / RNA polymerase II complex binding / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / site of DNA damage / RNA polymerase I complex / transcription elongation by RNA polymerase I / RNA polymerase III complex / response to UV / RNA polymerase II, core complex / tRNA transcription by RNA polymerase III / transcription by RNA polymerase I / transcription-coupled nucleotide-excision repair / DNA-directed RNA polymerase complex / transcription elongation factor complex / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / DNA-templated transcription initiation / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / ribonucleoside binding / fibrillar center / DNA-directed RNA polymerase / DNA-directed RNA polymerase activity / chromosome / protein-macromolecule adaptor activity / nucleic acid binding / transcription by RNA polymerase II / chromosome, telomeric region / protein ubiquitination / protein dimerization activity / nucleotide binding / RNA-directed RNA polymerase activity / DNA-templated transcription / chromatin binding / nucleolus / mitochondrion / DNA binding / zinc ion binding / nucleoplasm / metal ion binding / nucleus / cytosol 類似検索 - 分子機能
DNA-directed RNA polymerases I, II, and III subunit RPABC4 / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerase II subunit RPB4 / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta ...DNA-directed RNA polymerases I, II, and III subunit RPABC4 / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerase II subunit RPB4 / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta / DNA-directed RNA polymerases I, II, and III subunit RPABC1 / Transcription elongation factor 1 homolog / DNA-directed RNA polymerase II subunit RPB9 / UV-stimulated scaffold protein A 類似検索 - 構成要素
Netherlands Organisation for Scientific Research (NWO)
TOP 714.017.003
オランダ
Oncode Institute
オランダ
引用
ジャーナル: Mol Cell / 年: 2024 タイトル: STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment. 著者: Anisha R Ramadhin / Shun-Hsiao Lee / Di Zhou / Anita Salmazo / Camila Gonzalo-Hansen / Marjolein van Sluis / Cindy M A Blom / Roel C Janssens / Anja Raams / Dick Dekkers / Karel Bezstarosti / ...著者: Anisha R Ramadhin / Shun-Hsiao Lee / Di Zhou / Anita Salmazo / Camila Gonzalo-Hansen / Marjolein van Sluis / Cindy M A Blom / Roel C Janssens / Anja Raams / Dick Dekkers / Karel Bezstarosti / Dea Slade / Wim Vermeulen / Alex Pines / Jeroen A A Demmers / Carrie Bernecky / Titia K Sixma / Jurgen A Marteijn / 要旨: Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition ...Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4 ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment. However, the precise regulatory mechanisms of CRL4 activity and TFIIH recruitment remain elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a TC-NER factor, which is essential for correct DNA damage removal and subsequent transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA, UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability and CRL4 activity, resulting in efficient RNA Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core TC-NER component.
超分子 #1: Ternary complex of Pol II-TC-NER-STK19, focused on Pol II-ELOF1
超分子
名称: Ternary complex of Pol II-TC-NER-STK19, focused on Pol II-ELOF1 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Focused map contains Pol II, ELOF1 and the C-terminal parts of UVSSA.
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
理論値: 550 KDa
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分子 #1: DNA-directed RNA polymerase II subunit RPB1
UniProtKB: DNA-directed RNA polymerases I, II, and III subunit RPABC4
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分子 #13: Transcription elongation factor 1 homolog
分子
名称: Transcription elongation factor 1 homolog / タイプ: protein_or_peptide / ID: 13 詳細: The first two residues (Gly, Ala) are residual residues after TEV protease treatment. ELOF1 sequence starts from residue 3 (Met). 光学異性体: LEVO
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV
詳細
The final concentration of Pol II is around 0.15 mg/ml. The other components were added in different molar ratio. This sample was glutaraldehyde crosslinked.
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
特殊光学系
エネルギーフィルター - スリット幅: 20 eV
詳細
Collected on Krios 1 at Netherlands Center for Electron Nanoscopy (NeCEN)
撮影
フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 2 / 実像数: 13029 / 平均露光時間: 3.43 sec. / 平均電子線量: 50.0 e/Å2 詳細: Two datasets were collected from the same sample using the same parameters.