- EMDB-53243: RAD51 filament in complex with magnesium and ATP bound by the RAD... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-53243
タイトル
RAD51 filament in complex with magnesium and ATP bound by the RAD51AP1 C-terminus
マップデータ
試料
複合体: RAD51 filament in complex with magnesium and ATP bound by the RAD51AP1 C-terminus
タンパク質・ペプチド: DNA repair protein RAD51 homolog 1
タンパク質・ペプチド: RAD51-associated protein 1
DNA: DNA
リガンド: ADENOSINE-5'-TRIPHOSPHATE
リガンド: POTASSIUM ION
リガンド: MAGNESIUM ION
キーワード
RAD51 recombinase / RAD51AP1 / filament modulation / homologous recombination / nucleotide hydrolysis / DNA BINDING PROTEIN
機能・相同性
機能・相同性情報
D-loop DNA binding / positive regulation of reciprocal meiotic recombination / DNA secondary structure binding / presynaptic intermediate filament cytoskeleton / response to glucoside / mitotic recombination-dependent replication fork processing / DNA recombinase assembly / cellular response to camptothecin / chromosome organization involved in meiotic cell cycle / telomere maintenance via telomere lengthening ...D-loop DNA binding / positive regulation of reciprocal meiotic recombination / DNA secondary structure binding / presynaptic intermediate filament cytoskeleton / response to glucoside / mitotic recombination-dependent replication fork processing / DNA recombinase assembly / cellular response to camptothecin / chromosome organization involved in meiotic cell cycle / telomere maintenance via telomere lengthening / double-strand break repair involved in meiotic recombination / nuclear ubiquitin ligase complex / cellular response to cisplatin / DNA strand invasion / mitotic recombination / cellular response to hydroxyurea / replication-born double-strand break repair via sister chromatid exchange / DNA strand exchange activity / lateral element / regulation of DNA damage checkpoint / Impaired BRCA2 binding to PALB2 / telomere maintenance via recombination / single-stranded DNA helicase activity / reciprocal meiotic recombination / Homologous DNA Pairing and Strand Exchange / 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 / 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) / ATP-dependent DNA damage sensor activity / regulation of double-strand break repair via homologous recombination / nuclear chromosome / Impaired BRCA2 binding to RAD51 / Transcriptional Regulation by E2F6 / replication fork processing / Presynaptic phase of homologous DNA pairing and strand exchange / response to X-ray / ATP-dependent activity, acting on DNA / interstrand cross-link repair / positive regulation of double-strand break repair via homologous recombination / condensed chromosome / DNA polymerase binding / condensed nuclear chromosome / cellular response to ionizing radiation / male germ cell nucleus / meiotic cell cycle / cellular response to gamma radiation / double-strand break repair via homologous recombination / PML body / HDR through Homologous Recombination (HRR) / Meiotic recombination / response to toxic substance / single-stranded DNA binding / site of double-strand break / chromosome / double-stranded DNA binding / DNA recombination / chromosome, telomeric region / mitochondrial matrix / response to xenobiotic stimulus / DNA repair / DNA damage response / chromatin binding / centrosome / chromatin / nucleolus / perinuclear region of cytoplasm / enzyme binding / ATP hydrolysis activity / protein-containing complex / mitochondrion / DNA binding / RNA binding / nucleoplasm / ATP binding / identical protein binding / nucleus / cytoplasm / cytosol 類似検索 - 分子機能
RAD51 interacting motif / : / RAD51 interacting motif / DNA recombination/repair protein Rad51 / DNA recombination and repair protein, RecA-like / DNA recombination and repair protein Rad51-like, C-terminal / Rad51 / DNA recombination and repair protein RecA, monomer-monomer interface / RecA family profile 2. / DNA recombination and repair protein RecA-like, ATP-binding domain ...RAD51 interacting motif / : / RAD51 interacting motif / DNA recombination/repair protein Rad51 / DNA recombination and repair protein, RecA-like / DNA recombination and repair protein Rad51-like, C-terminal / Rad51 / DNA recombination and repair protein RecA, monomer-monomer interface / RecA family profile 2. / DNA recombination and repair protein RecA-like, ATP-binding domain / RecA family profile 1. / DNA repair Rad51/transcription factor NusA, alpha-helical / Helix-hairpin-helix domain / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
DNA repair protein RAD51 homolog 1 / RAD51-associated protein 1 類似検索 - 構成要素
ジャーナル: Proc Natl Acad Sci U S A / 年: 2025 タイトル: RAD51AP1 is a versatile RAD51 modulator. 著者: Lucas Kuhlen / Bilge Argunhan / Pengtao Liang / Janet Zhong / Laura Masino / Xiaodong Zhang / 要旨: RAD51AP1 is an emergent key factor in homologous recombination (HR), the major pathway for accurate repair of DNA double-strand breaks, and in alternative lengthening of telomeres (ALT). Depletion of ...RAD51AP1 is an emergent key factor in homologous recombination (HR), the major pathway for accurate repair of DNA double-strand breaks, and in alternative lengthening of telomeres (ALT). Depletion of RAD51AP1 diminishes HR and overexpression is common in cancer, where it is associated with malignancy. Here, we show that RAD51AP1 has a hitherto unknown role in modulating the RAD51 recombinase, the central player in HR. Through a combination of biochemistry and structural biology, we reveal that RAD51AP1 possesses at least three RAD51-binding sites that facilitate its binding across two adjacent RAD51 molecules. We uncover a previously unidentified RAD51-binding mode that stabilizes the RAD51 N-terminal domain and protomer interface in the filaments. We uncover a previously undescribed role for RAD51AP1 in stabilizing RAD51-ssDNA filaments and promoting strand exchange. Our structural data provide the molecular basis for how RAD51AP1 binding induces conformational changes that promote RAD51 DNA association and oligomerization, therefore promoting filament nucleation, stabilization, and strand exchange. Further, we resolved structures of RAD51-ssDNA filaments in the presence of Mg-ATP and upon hydrolysis to Mg-ADP, revealing that RAD51 filaments expand upon ATP hydrolysis and explaining how ADP reduces RAD51-DNA binding. Our findings reveal RAD51AP1 as a versatile RAD51 modulator and RAD51 filament remodeler and shed previously unidentified insights into the modulation of HR, which is critical for the maintenance of genome stability.