DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation. / Kwon, Youngho; Rösner, Heike; Zhao, Weixing; Selemenakis, Platon; He, Zhuoling; Kawale, Ajinkya S; Katz, Jeffrey N; Rogers, Cody M; Neal, Francisco E; Badamchi Shabestari, Aida; Petrosius, Valdemaras; Singh, Akhilesh K; Joel, Marina Z; Lu, Lucy; Holloway, Stephen P; Burma, Sandeep; Mukherjee, Bipasha; Hromas, Robert; Mazin, Alexander; Wiese, Claudia; Sørensen, Claus S.; Sung, Patrick.

In: Nature Communications, Vol. 14, 432, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kwon, Y, Rösner, H, Zhao, W, Selemenakis, P, He, Z, Kawale, AS, Katz, JN, Rogers, CM, Neal, FE, Badamchi Shabestari, A, Petrosius, V, Singh, AK, Joel, MZ, Lu, L, Holloway, SP, Burma, S, Mukherjee, B, Hromas, R, Mazin, A, Wiese, C, Sørensen, CS & Sung, P 2023, 'DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation', Nature Communications, vol. 14, 432. https://doi.org/10.1038/s41467-023-36211-x

APA

Kwon, Y., Rösner, H., Zhao, W., Selemenakis, P., He, Z., Kawale, A. S., Katz, J. N., Rogers, C. M., Neal, F. E., Badamchi Shabestari, A., Petrosius, V., Singh, A. K., Joel, M. Z., Lu, L., Holloway, S. P., Burma, S., Mukherjee, B., Hromas, R., Mazin, A., ... Sung, P. (2023). DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation. Nature Communications, 14, [432]. https://doi.org/10.1038/s41467-023-36211-x

Vancouver

Kwon Y, Rösner H, Zhao W, Selemenakis P, He Z, Kawale AS et al. DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation. Nature Communications. 2023;14. 432. https://doi.org/10.1038/s41467-023-36211-x

Author

Kwon, Youngho ; Rösner, Heike ; Zhao, Weixing ; Selemenakis, Platon ; He, Zhuoling ; Kawale, Ajinkya S ; Katz, Jeffrey N ; Rogers, Cody M ; Neal, Francisco E ; Badamchi Shabestari, Aida ; Petrosius, Valdemaras ; Singh, Akhilesh K ; Joel, Marina Z ; Lu, Lucy ; Holloway, Stephen P ; Burma, Sandeep ; Mukherjee, Bipasha ; Hromas, Robert ; Mazin, Alexander ; Wiese, Claudia ; Sørensen, Claus S. ; Sung, Patrick. / DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation. In: Nature Communications. 2023 ; Vol. 14.

Bibtex

@article{95674b82f17e48218f1d29a05bec874a,
title = "DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation",
abstract = "The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.",
keywords = "DNA Replication, Rad51 Recombinase/genetics, DNA Repair, BRCA2 Protein/metabolism, DNA, Homologous Recombination",
author = "Youngho Kwon and Heike R{\"o}sner and Weixing Zhao and Platon Selemenakis and Zhuoling He and Kawale, {Ajinkya S} and Katz, {Jeffrey N} and Rogers, {Cody M} and Neal, {Francisco E} and {Badamchi Shabestari}, Aida and Valdemaras Petrosius and Singh, {Akhilesh K} and Joel, {Marina Z} and Lucy Lu and Holloway, {Stephen P} and Sandeep Burma and Bipasha Mukherjee and Robert Hromas and Alexander Mazin and Claudia Wiese and S{\o}rensen, {Claus S.} and Patrick Sung",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-36211-x",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation

AU - Kwon, Youngho

AU - Rösner, Heike

AU - Zhao, Weixing

AU - Selemenakis, Platon

AU - He, Zhuoling

AU - Kawale, Ajinkya S

AU - Katz, Jeffrey N

AU - Rogers, Cody M

AU - Neal, Francisco E

AU - Badamchi Shabestari, Aida

AU - Petrosius, Valdemaras

AU - Singh, Akhilesh K

AU - Joel, Marina Z

AU - Lu, Lucy

AU - Holloway, Stephen P

AU - Burma, Sandeep

AU - Mukherjee, Bipasha

AU - Hromas, Robert

AU - Mazin, Alexander

AU - Wiese, Claudia

AU - Sørensen, Claus S.

AU - Sung, Patrick

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.

AB - The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.

KW - DNA Replication

KW - Rad51 Recombinase/genetics

KW - DNA Repair

KW - BRCA2 Protein/metabolism

KW - DNA

KW - Homologous Recombination

U2 - 10.1038/s41467-023-36211-x

DO - 10.1038/s41467-023-36211-x

M3 - Journal article

C2 - 36702902

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 432

ER -

ID: 336451096