Your browser doesn't support javascript.
loading
Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry.
Zhao, Weixing; Vaithiyalingam, Sivaraja; San Filippo, Joseph; Maranon, David G; Jimenez-Sainz, Judit; Fontenay, Gerald V; Kwon, Youngho; Leung, Stanley G; Lu, Lucy; Jensen, Ryan B; Chazin, Walter J; Wiese, Claudia; Sung, Patrick.
Affiliation
  • Zhao W; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Vaithiyalingam S; Departments of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
  • San Filippo J; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Maranon DG; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
  • Jimenez-Sainz J; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Fontenay GV; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Kwon Y; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Leung SG; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Lu L; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Jensen RB; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Chazin WJ; Departments of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: walter.chazin@vanderbilt.edu.
  • Wiese C; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Sung P; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: patrick.sung@yale.edu.
Mol Cell ; 59(2): 176-87, 2015 Jul 16.
Article in En | MEDLINE | ID: mdl-26145171
ABSTRACT
The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: BRCA2 Protein / Proteasome Endopeptidase Complex / Replication Protein A / Homologous Recombination Type of study: Prognostic_studies Limits: Female / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2015 Type: Article Affiliation country: United States
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: BRCA2 Protein / Proteasome Endopeptidase Complex / Replication Protein A / Homologous Recombination Type of study: Prognostic_studies Limits: Female / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2015 Type: Article Affiliation country: United States