- EMDB-31020: Structural insight into BRCA1-BARD1 complex recruitment to damage... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-31020
タイトル
Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin
マップデータ
試料
複合体: BARD1-NCP-Ubiquitin complex
複合体: DNA
DNA: DNA (145-MER)
DNA: DNA (145-MER)
複合体: Histone
タンパク質・ペプチド: Histone H3
タンパク質・ペプチド: Histone H4
タンパク質・ペプチド: Histone H2A
タンパク質・ペプチド: Histone H2B 1.1
複合体: BARD1-Ubiquitin
タンパク質・ペプチド: BRCA1-associated RING domain protein 1
タンパク質・ペプチド: Polyubiquitin-B
キーワード
BRCA1 / nucleosome / DNA damage / chromatin / BARD1 / NUCLEAR PROTEIN
機能・相同性
機能・相同性情報
negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / nuclear ubiquitin ligase complex / DNA strand resection involved in replication fork processing / homologous recombination ...negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / nuclear ubiquitin ligase complex / DNA strand resection involved in replication fork processing / homologous recombination / tissue homeostasis / protein K6-linked ubiquitination / regulation of DNA damage checkpoint / regulation of phosphorylation / Impaired BRCA2 binding to PALB2 / mitotic G2/M transition checkpoint / negative regulation of protein export from nucleus / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cell cycle / regulation of DNA repair / ubiquitin ligase complex / cellular response to ionizing radiation / Nonhomologous End-Joining (NHEJ) / RING-type E3 ubiquitin transferase / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / Metalloprotease DUBs / kinase binding / cytoplasmic ribonucleoprotein granule / positive regulation of protein catabolic process / structural constituent of chromatin / ubiquitin-protein transferase activity / UCH proteinases / nucleosome / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / regulation of cell cycle / protein ubiquitination / nuclear speck / positive regulation of apoptotic process / protein heterodimerization activity / DNA repair / DNA damage response / negative regulation of apoptotic process / protein homodimerization activity / DNA binding / RNA binding / nucleoplasm / nucleus / metal ion binding / cytoplasm 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
31671344
中国
National Natural Science Foundation of China (NSFC)
31871318
中国
National Natural Science Foundation of China (NSFC)
31970621
中国
National Natural Science Foundation of China (NSFC)
31801070
中国
National Natural Science Foundation of China (NSFC)
31730021
中国
National Natural Science Foundation of China (NSFC)
31971220
中国
National Natural Science Foundation of China (NSFC)
3170040161
中国
National Natural Science Foundation of China (NSFC)
31961160725
中国
引用
ジャーナル: Mol Cell / 年: 2021 タイトル: Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin. 著者: Linchang Dai / Yaxin Dai / Jinhua Han / Yan Huang / Longge Wang / Jun Huang / Zheng Zhou / 要旨: The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites ...The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites requires BARD1-mediated nucleosome interaction and histone mark recognition. Here, we report the cryo-EM structure of BARD1 bound to a ubiquitinated nucleosome core particle (NCP) at 3.1 Å resolution and illustrate how BARD1 simultaneously recognizes the DNA damage-induced mark H2AK15ub and DNA replication-associated mark H4K20me0 on the nucleosome. In vitro and in vivo analyses reveal that the BARD1-NCP complex is stabilized by BARD1-nucleosome interaction, BARD1-ubiquitin interaction, and BARD1 ARD domain-BARD1 BRCT domain interaction, and abrogating these interactions is detrimental to HR activity. We further identify multiple disease-causing BARD1 mutations that disrupt BARD1-NCP interactions and hence impair HR. Together, this study elucidates the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes and sheds important light on cancer therapeutic avenues.