8A51

Crystal structure of HSF2BP-BRME1 complex

Summary for 8A51

• Entry DOI: 10.2210/pdb8a51/pdb
• Descriptor: Heat shock factor 2-binding protein, Break repair meiotic recombinase recruitment factor 1, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: complex, recombination
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 9177.11

Authors

Miron, S.,Legrand, P.,Ropars, V.,Ghouil, R.,Zinn-Justin, S. (deposition date: 2022-06-13, release date: 2023-07-05, Last modification date: 2024-05-01)

Primary citation

Ghouil, R.,Miron, S.,Sato, K.,Ristic, D.,van Rossum-Fikkert, S.E.,Legrand, P.,Ouldali, M.,Winter, J.M.,Ropars, V.,David, G.,Arteni, A.A.,Wyman, C.,Knipscheer, P.,Kanaar, R.,Zelensky, A.N.,Zinn-Justin, S.
BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination.
Sci Adv, 9:eadi7352-eadi7352, 2023

PubMed Abstract: 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.

PubMed: 37889963
DOI: 10.1126/sciadv.adi7352

Experimental method

X-RAY DIFFRACTION (1.9 Å)