ジャーナル: Sci Adv / 年: 2023 タイトル: BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination. 著者: Rania Ghouil / Simona Miron / Koichi Sato / Dejan Ristic / Sari E van Rossum-Fikkert / Pierre Legrand / Malika Ouldali / Jean-Marie Winter / Virginie Ropars / Gabriel David / Ana-Andreea ...著者: Rania Ghouil / Simona Miron / Koichi Sato / Dejan Ristic / Sari E van Rossum-Fikkert / Pierre Legrand / Malika Ouldali / Jean-Marie Winter / Virginie Ropars / Gabriel David / Ana-Andreea Arteni / Claire Wyman / Puck Knipscheer / Roland Kanaar / Alex N Zelensky / Sophie Zinn-Justin / 要旨: In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). The HSF2BP-BRME1 complex interacts with BRCA2. Its ...In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). The HSF2BP-BRME1 complex interacts with BRCA2. Its absence causes a severe reduction in recombinase loading at meiotic DSB. We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-mer. Addition of BRME1 leads to dissociation of both of these ring structures and cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage. It also prevents BRCA2 degradation during interstrand DNA crosslink repair in egg extracts. We propose that, during meiosis, the control of HSF2BPBRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.
全体 : Complex between HSF2BP and the BRCA2 fragment N2291-Q2342
全体
名称: Complex between HSF2BP and the BRCA2 fragment N2291-Q2342
要素
複合体: Complex between HSF2BP and the BRCA2 fragment N2291-Q2342
タンパク質・ペプチド: HSF2BP
タンパク質・ペプチド: BRCA2
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超分子 #1: Complex between HSF2BP and the BRCA2 fragment N2291-Q2342
超分子
名称: Complex between HSF2BP and the BRCA2 fragment N2291-Q2342 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: The complex contains 24 HSF2BP molecules and 12 BRCA2 peptides
クラス数: 3 / ソフトウェア - 名称: cryoSPARC 詳細: One of these volumes had the shape of an open ring, the two other volumes were well-resolved rings. The 398 000 particles corresponding to these two volumes were used to calculate the final ...詳細: One of these volumes had the shape of an open ring, the two other volumes were well-resolved rings. The 398 000 particles corresponding to these two volumes were used to calculate the final cryo-EM map of the complex.