DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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.
I: Nature Communications, Bind 14, 432, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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