BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination

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

doi:10.1126/sciadv.adi7352

BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

2 Citations (Scopus)

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-nucleotide oligomer. 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 Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.

Original language	English
Pages (from-to)	eadi7352
Journal	Science advances
Volume	9
Issue number	43
DOIs	https://doi.org/10.1126/sciadv.adi7352
Publication status	Published - 27 Oct 2023

Keywords

Rad51 Recombinase/genetics
Homologous Recombination
DNA Repair
DNA-Binding Proteins/metabolism
DNA Damage

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10.1126/sciadv.adi7352

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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. (2023). BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination. Science advances, 9(43), eadi7352. https://doi.org/10.1126/sciadv.adi7352

@article{8288d6af54964b94aa473290dd8745bc,

title = "BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination",

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-nucleotide oligomer. 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 Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.",

keywords = "Rad51 Recombinase/genetics, Homologous Recombination, DNA Repair, DNA-Binding Proteins/metabolism, DNA Damage",

author = "Rania Ghouil and Simona Miron and Koichi Sato and Dejan Ristic and {van Rossum-Fikkert}, {Sari E} and Pierre Legrand and Malika Ouldali and Jean-Marie Winter and Virginie Ropars and Gabriel David and Ana-Andreea Arteni and Claire Wyman and Puck Knipscheer and Roland Kanaar and Zelensky, {Alex N} and Sophie Zinn-Justin",

year = "2023",

month = oct,

day = "27",

doi = "10.1126/sciadv.adi7352",

language = "English",

volume = "9",

pages = "eadi7352",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "43",

}

Ghouil, R, Miron, S, Sato, K, Ristic, D, van Rossum-Fikkert, SE, Legrand, P, Ouldali, M, Winter, J-M, Ropars, V, David, G, Arteni, A-A, Wyman, C, Knipscheer, P, Kanaar, R, Zelensky, AN & Zinn-Justin, S 2023, 'BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination', Science advances, vol. 9, no. 43, pp. eadi7352. https://doi.org/10.1126/sciadv.adi7352

TY - JOUR

T1 - BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination

AU - Ghouil, Rania

AU - Miron, Simona

AU - Sato, Koichi

AU - Ristic, Dejan

AU - van Rossum-Fikkert, Sari E

AU - Legrand, Pierre

AU - Ouldali, Malika

AU - Winter, Jean-Marie

AU - Ropars, Virginie

AU - David, Gabriel

AU - Arteni, Ana-Andreea

AU - Wyman, Claire

AU - Knipscheer, Puck

AU - Kanaar, Roland

AU - Zelensky, Alex N

AU - Zinn-Justin, Sophie

PY - 2023/10/27

Y1 - 2023/10/27

N2 - 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-nucleotide oligomer. 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 Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.

AB - 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-nucleotide oligomer. 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 Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.

KW - Rad51 Recombinase/genetics

KW - Homologous Recombination

KW - DNA Repair

KW - DNA-Binding Proteins/metabolism

KW - DNA Damage

U2 - 10.1126/sciadv.adi7352

DO - 10.1126/sciadv.adi7352

M3 - Article

C2 - 37889963

SN - 2375-2548

VL - 9

SP - eadi7352

JO - Science advances

JF - Science advances

IS - 43

ER -

BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination

Abstract

Keywords

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