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データを開く
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | OGG1 bound to a nucleosome containing 8oxoG at SHL-6 (composite map) | |||||||||
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![]() | Nucleosome / 8-oxo-guanine DNA Glycosylase I / DNA Repair / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex | |||||||||
機能・相同性 | ![]() Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / depyrimidination / 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity / Displacement of DNA glycosylase by APEX1 ...Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / depyrimidination / 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity / Displacement of DNA glycosylase by APEX1 / positive regulation of gene expression via chromosomal CpG island demethylation / oxidized purine DNA binding / 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素 / APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere organization / Interleukin-7 signaling / Inhibition of DNA recombination at telomere / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / RNA Polymerase I Promoter Opening / Meiotic synapsis / DNA-(apurinic or apyrimidinic site) lyase / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / SIRT1 negatively regulates rRNA expression / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / innate immune response in mucosa / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / cellular response to reactive oxygen species / nucleotide-excision repair / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / response to radiation / HDMs demethylate histones / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / base-excision repair / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / nuclear matrix / Transcriptional regulation of granulopoiesis / HCMV Early Events / antimicrobial humoral immune response mediated by antimicrobial peptide / structural constituent of chromatin / UCH proteinases / antibacterial humoral response / nucleosome / heterochromatin formation / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / HATs acetylate histones / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / chromatin organization / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Processing of DNA double-strand break ends / Senescence-Associated Secretory Phenotype (SASP) / endonuclease activity / Oxidative Stress Induced Senescence / microtubule binding / Estrogen-dependent gene expression / response to oxidative stress / gene expression / damaged DNA binding / chromosome, telomeric region / defense response to Gram-positive bacterium / Ub-specific processing proteases / nuclear speck / mitochondrial matrix / RNA polymerase II cis-regulatory region sequence-specific DNA binding 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
![]() | Weaver TM / Ling JA / Freudenthal BD | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Contributing factors to the oxidation-induced mutational landscape in human cells. 著者: Cameron Cordero / Kavi P M Mehta / Tyler M Weaver / Justin A Ling / Bret D Freudenthal / David Cortez / Steven A Roberts / ![]() 要旨: 8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently ...8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers. Potassium bromate (KBrO)-induced 8-oxoGs occur with similar sequence preferences as their derived substitutions, indicating that the reactivity of specific oxidants dictates mutation sequence specificity. While 8-oxoG occurs uniformly across chromatin, 8-oxoG-induced mutations are elevated in compact genomic regions, within nucleosomes, and at inward facing guanines within strongly positioned nucleosomes. Cryo-electron microscopy structures of OGG1-nucleosome complexes indicate that these effects originate from OGG1's ability to flip outward positioned 8-oxoG lesions into the catalytic pocket while inward facing lesions are occluded by the histone octamer. Mutation spectra from human cells with DNA repair deficiencies reveals contributions of a DNA repair network limiting 8-oxoG mutagenesis, where OGG1- and MUTYH-mediated base excision repair is supplemented by the replication-associated factors Pol η and HMCES. Transcriptional asymmetry of KBrO-induced mutations in OGG1- and Pol η-deficient cells also demonstrates transcription-coupled repair can prevent 8-oxoG-induced mutation. Thus, oxidant chemistry, chromatin structures, and DNA repair processes combine to dictate the oxidative mutational landscape in human genomes. | |||||||||
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 393 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.6 KB 19.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 100.8 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 505.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 505.1 KB | 表示 | |
XML形式データ | ![]() | 8.8 KB | 表示 | |
CIF形式データ | ![]() | 10.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.534 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : OGG1 bound to a nucleosome containing 8oxoG at SHL-6 (composite map)
全体 | 名称: OGG1 bound to a nucleosome containing 8oxoG at SHL-6 (composite map) |
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要素 |
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-超分子 #1: OGG1 bound to a nucleosome containing 8oxoG at SHL-6 (composite map)
超分子 | 名称: OGG1 bound to a nucleosome containing 8oxoG at SHL-6 (composite map) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#7 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Histone H3.2
分子 | 名称: Histone H3.2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 15.257838 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: ARTKQTARKS TGGKAPRKQL ATKAARKSAP ATGGVKKPHR YRPGTVALRE IRRYQKSTEL LIRKLPFQRL VREIAQDFKT DLRFQSSAV MALQEASEAY LVGLFEDTNL AAIHAKRVTI MPKDIQLARR IRGERA UniProtKB: Histone H3.2 |
-分子 #2: Histone H4
分子 | 名称: Histone H4 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 11.263231 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SGRGKGGKGL GKGGAKRHRK VLRDNIQGIT KPAIRRLARR GGVKRISGLI YEETRGVLKV FLENVIRDAV TYTEHAKRKT VTAMDVVYA LKRQGRTLYG FGG UniProtKB: Histone H4 |
-分子 #3: Histone H2A type 1
分子 | 名称: Histone H2A type 1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 13.990342 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SGRGKQGGKA RAKAKTRSSR AGLQFPVGRV HRLLRKGNYA ERVGAGAPVY LAAVLEYLTA EILELAGNAA RDNKKTRIIP RHLQLAIRN DEELNKLLGK VTIAQGGVLP NIQAVLLPKK TESHHKAKGK UniProtKB: Histone H2A type 1 |
-分子 #4: Histone H2B type 1-C/E/F/G/I
分子 | 名称: Histone H2B type 1-C/E/F/G/I / タイプ: protein_or_peptide / ID: 4 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 13.806018 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: PEPAKSAPAP KKGSKKAVTK AQKKDGKKRK RSRKESYSVY VYKVLKQVHP DTGISSKAMG IMNSFVNDIF ERIAGEASRL AHYNKRSTI TSREIQTAVR LLLPGELAKH AVSEGTKAVT KYTSSK UniProtKB: Histone H2B type 1-C/E/F/G/I |
-分子 #7: N-glycosylase/DNA lyase
分子 | 名称: N-glycosylase/DNA lyase / タイプ: protein_or_peptide / ID: 7 / コピー数: 1 / 光学異性体: LEVO EC番号: 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 38.833113 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MPARALLPRR MGHRTLASTP ALWASIPCPR SELRLDLVLP SGQSFRWREQ SPAHWSGVLA DQVWTLTQTE EQLHCTVYRG DKSQASRPT PDELEAVRKY FQLDVTLAQL YHHWGSVDSH FQEVAQKFQG VRLLRQDPIE CLFSFICSSN NNIARITGMV E RLCQAFGP ...文字列: MPARALLPRR MGHRTLASTP ALWASIPCPR SELRLDLVLP SGQSFRWREQ SPAHWSGVLA DQVWTLTQTE EQLHCTVYRG DKSQASRPT PDELEAVRKY FQLDVTLAQL YHHWGSVDSH FQEVAQKFQG VRLLRQDPIE CLFSFICSSN NNIARITGMV E RLCQAFGP RLIQLDDVTY HGFPSLQALA GPEVEAHLRK LGLGYRARYV SASARAILEE QGGLAWLQQL RESSYEEAHK AL CILPGVG TQVADCICLM ALDKPQAVPV DVHMWHIAQR DYSWHPTTSQ AKGPSPQTNK ELGNFFRSLW GPYAGWAQAV LFS ADLRQS RHAQEPPAKR RKGSKGPEG UniProtKB: N-glycosylase/DNA lyase |
-分子 #5: 601 I strand (non-damaged strand)
分子 | 名称: 601 I strand (non-damaged strand) / タイプ: dna / ID: 5 / コピー数: 1 / 分類: DNA |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 45.114742 KDa |
配列 | 文字列: (DA)(DT)(DC)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA) (DA)(DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA) (DG) (DA)(DC)(DA)(DG)(DC) ...文字列: (DA)(DT)(DC)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA) (DA)(DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA) (DG) (DA)(DC)(DA)(DG)(DC)(DT)(DC)(DT) (DA)(DG)(DC)(DA)(DC)(DC)(DG)(DC)(DT)(DT) (DA)(DA) (DA)(DC)(DG)(DC)(DA)(DC)(DG) (DT)(DA)(DC)(DG)(DC)(DG)(DC)(DT)(DG)(DT) (DC)(DC)(DC) (DC)(DC)(DG)(DC)(DG)(DT) (DT)(DT)(DT)(DA)(DA)(DC)(DC)(DG)(DC)(DC) (DA)(DA)(DG)(DG) (DG)(DG)(DA)(DT)(DT) (DA)(DC)(DT)(DC)(DC)(DC)(DT)(DA)(DG)(DT) (DC)(DT)(DC)(DC)(DA) (DG)(DG)(DC)(DA) (DC)(DG)(DT)(DG)(DT)(DC)(DA)(DG)(DA)(DT) (DC)(DT)(DA)(DT)(DA)(DC) (DA)(DT)(DC) (DC)(DG)(DA)(DT) |
-分子 #6: 601 J strand (damaged strand)
分子 | 名称: 601 J strand (damaged strand) / タイプ: dna / ID: 6 / コピー数: 1 / 分類: DNA |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 45.651059 KDa |
配列 | 文字列: (DA)(DT)(DC)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(8OG)(DA)(DT)(DC)(DT)(DG)(DA) (DC)(DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG) (DG)(DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG) (DA)(DG)(DT)(DA)(DA)(DT) ...文字列: (DA)(DT)(DC)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(8OG)(DA)(DT)(DC)(DT)(DG)(DA) (DC)(DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG) (DG)(DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG) (DA)(DG)(DT)(DA)(DA)(DT)(DC)(DC)(DC) (DC)(DT)(DT)(DG)(DG)(DC)(DG)(DG)(DT)(DT) (DA) (DA)(DA)(DA)(DC)(DG)(DC)(DG)(DG) (DG)(DG)(DG)(DA)(DC)(DA)(DG)(DC)(DG)(DC) (DG)(DT) (DA)(DC)(DG)(DT)(DG)(DC)(DG) (DT)(DT)(DT)(DA)(DA)(DG)(DC)(DG)(DG)(DT) (DG)(DC)(DT) (DA)(DG)(DA)(DG)(DC)(DT) (DG)(DT)(DC)(DT)(DA)(DC)(DG)(DA)(DC)(DC) (DA)(DA)(DT)(DT) (DG)(DA)(DG)(DC)(DG) (DG)(DC)(DC)(DT)(DC)(DG)(DG)(DC)(DA)(DC) (DC)(DG)(DG)(DG)(DA) (DT)(DT)(DC)(DT) (DC)(DG)(DA)(DT) |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.1 構成要素:
詳細: 50 mM HEPES (pH-7.1), 100 mM NaCl, 1 mM TCEP, and 1 mM EDTA | |||||||||||||||
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 277.15 K |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 32685 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC (ver. v4.3) |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC (ver. v4.3) |