ArticleNature communications2023
DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47citing papers in PubMed
10.3field-weighted citation impact, top 1% of its field
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47 citing papers in PubMed, 61 citations in OpenAlex.
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.NAR cancer · 2026Article
- PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy.Materials today. Bio · 2026Article
- HELZ-BRCA2 complex resolves R-loops to drive transcription-coupled homologous recombination.Nature communications · 2026Article
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.bioRxiv : the preprint server for biology · 2026Article
- Decoding the Transcriptional Complexity of the Human BRCA2 DNA Repair Gene Using Hybrid-seq.Biochemical genetics · 2026Article
- Multifaceted roles of PDS5B in RAD51-dependent homology-directed DNA repair and replication fork protection.Nature communications · 2026Article
- BRCA1/2 Reversion Mutations in Japanese Patients with Metastatic Breast Cancer Progressing on Olaparib: OLIVE (WJOG15321B).Breast cancer (Tokyo, Japan) · 2026Observational
- Mechanism of single-strand annealing from native mass spectrometry and cryo-EM structures of RAD52 homolog Mgm101.Nucleic acids research · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Chromatin accessibility regulates age-dependent nuclear mechanotransduction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TONSL promotes hepatocellular carcinoma progression and radioresistance by orchestrating DNA damage repair and cell cycle dynamics.Discover oncology · 2026Article
- Neural Latent Filtering for Gene Discovery in Breast Cancer Subtypes.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Modeling mammalian meiosis with pluripotent stem cells: progress and challenges.Clinical epigenetics · 2026Review
- A single BRCA2 BRC repeat supports viability while multiple repeats ensure resilience under stress.bioRxiv : the preprint server for biology · 2026Article
- Three-dimensional-bioprinted stiff matrix triggers PDAC radioresistance through histone H3 lysine 18 lactylation (H3K18la) potentiates RAD51 activation.Regenerative biomaterials · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Modelling DMC1 mediated homologous recombination repair in mouse embryonic stem cells.Frontiers in cell and developmental biology · 2026Article
- Mechanism of single-strand annealing from native mass spectrometry and cryo-EM structures of RAD52 homolog Mgm101.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA.Nucleic acids research · 2025Article
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Authors and funding
22 authors at 7 institutions in 2 countries.
Youngho Kwon *Department of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.ORCID 0000-0002-0287-8795
Heike Rösner *Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark.ORCID 0000-0002-6201-3195
Weixing ZhaoDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Platon SelemenakisDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.ORCID 0000-0002-4507-2249
Zhuoling HeDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Ajinkya S KawaleDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Jeffrey N KatzDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Cody M RogersDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Francisco E NealDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.ORCID 0000-0001-7676-8997
Aida Badamchi ShabestariDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Valdemaras PetrosiusBiotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
Akhilesh K SinghDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0001-6739-6079
Marina Z JoelDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
Lucy LuDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
Stephen P HollowayDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Sandeep BurmaDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.ORCID 0000-0001-7057-9845
Bipasha MukherjeeDepartment of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Robert HromasDepartment of Medicine, University of Texas Health at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
Alexander MazinDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Claudia WieseDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA. claudia.wiese@colostate.edu.ORCID 0000-0001-6844-4693
Claus S SørensenBiotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark. claus.storgaard@bric.ku.dk.ORCID 0000-0001-6022-9710
Patrick SungDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA. sungp@uthscsa.edu.ORCID 0000-0003-1396-9040
The University of Texas Health Science Center at San Antonio · USUniversity of Copenhagen · DKYale University · USColorado State University · USHarvard University · USJohns Hopkins University · USThe University of Texas MD Anderson Cancer Center · US
Funding
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6MTRAINING GRANT ON THE BIOLOGY OF AGINGT32AG021890 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Erzsebet Kokovay, JAMES FLOYD NELSON · 2003 to 2026
$11.4MYEAST DNA REPAIR GENES AND PROTEINS OF THE RAD52 GROUPR01ES007061 · NIEHS · YALE UNIVERSITY · PI Patrick Sung · 1995 to 2026
$9.4MMechanisms of DNA Homology-directed Genome Repair and Tumor SuppressionR35CA241801 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUNG, PATRICK · 2019 to 2025
$6.0MMechanistic Dissection of the Fanconi Anemia Pathway of DNA Damage Response and RR01CA168635 · NCI · YALE UNIVERSITY · PI Gary M Kupfer, Patrick Sung · 2013 to 2026
$5.8MCancer Biology Training ProgramT32CA148724 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Pei Wang, Feng-Chun Yang · 2011 to 2026
$3.3MEEPD1 Repair of Stressed Replication ForksR01CA205224 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robert A Hromas · 2016 to 2026
$3.3MAML mutation-guided drugging of DNA repairR01CA237286 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI MAZIN, ALEXANDER V, SKORSKI, TOMASZ · 2020 to 2024
$2.8MBladder cancer PD-L1 control of homologous recombination: Basic mechanisms applied to novel treatmentsR01CA268641 · NCI · DARTMOUTH-HITCHCOCK CLINIC · PI Tyler J. Curiel, WEIXING Wilson ZHAO · 2022 to 2026
$2.5MSmall Molecule inhibitors as a new approach to study human RAD51 recombinaseR01CA188347 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MAZIN, ALEXANDER V · 2015 to 2019
$2.5MMechanisms of RNA-dependent DNA repair in humansR01GM136717 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MAZIN, ALEXANDER V · 2020 to 2023
$1.8MRadiation-induced senescence in the brain microenvironment: Implications for glioblastoma recurrence and therapyR01CA246807 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BURMA, SANDEEP · 2021 to 2025
$1.8MNCI NIH HHS F30 CA260908NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA168635NCI NIH HHS R01 CA188347NCI NIH HHS R01 CA205224NCI NIH HHS R01 CA237286NCI NIH HHS R01 CA246807NCI NIH HHS R01 CA268641NCI NIH HHS R35 CA241801NCI NIH HHS R50 CA265315NCI NIH HHS T32 CA148724NIA NIH HHS T32 AG021890NIEHS NIH HHS R01 ES007061NIEHS NIH HHS R56 ES021454NIGMS NIH HHS R01 GM136717NIGMS NIH HHS R01 GM141091
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.
Indexed as
DNA ReplicationRad51 RecombinaseBRCA2 ProteinDNADNA RepairHomologous RecombinationBRCA2 ProteinDNARad51 Recombinase
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