Investigating the Role of the BRCA2 C‐Terminus in Homologous Recombination
The tumor suppressor protein, BRCA2, acts as a mediator for DNA double stranded break repair via homologous recombination (HR). Mutations in BRCA2 lead to a higher risk of tumor formation, particularly in breast and ovarian cancers. The C‐terminus of BRCA2 plays an important role in the protein'...
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| Published in: | The FASEB journal Vol. 32; no. S1; p. lb211 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
The Federation of American Societies for Experimental Biology
01-04-2018
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| Online Access: | Get full text |
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| Summary: | The tumor suppressor protein, BRCA2, acts as a mediator for DNA double stranded break repair via homologous recombination (HR). Mutations in BRCA2 lead to a higher risk of tumor formation, particularly in breast and ovarian cancers. The C‐terminus of BRCA2 plays an important role in the protein's overall ability to bind to DNA during HR. Of the identified tumor associated BRCA2 mutations, 27% are found in the C‐terminus, suggesting the significance of this region in tumor suppression. An important function of the C‐terminus is the ability to bind DSS1, a small, acidic protein found to be critical for DNA repair. DSS1 supports the stability of BRCA2 and is thought to act as a DNA mimic, dissociating replication protein A (RPA) from single stranded DNA (ssDNA). As RPA dissociates, the ssDNA becomes available for RAD51 binding and nucleoprotein filament formation leading to the repair of damaged DNA. When DSS1 is altered or absent, BRCA2 is unable to promote dissociation of RPA from ssDNA and a decrease in HR efficiency is observed. The Pingry School SMART Team, in conjunction with MSOE Center for BioMolecular Modeling, used 3D modeling and printing technology to examine the structure‐function relationship of BRCA2, DSS1, and ssDNA. While further research is necessary to more completely characterize the roles of DSS1 and the BRCA2 C‐terminus in HR, the Pingry School SMART Team model aims to describe the structural relationship between these proteins.
Support or Funding Information
This work was supported by The Pingry School.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal. |
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| ISSN: | 0892-6638 1530-6860 |
| DOI: | 10.1096/fasebj.2018.32.1_supplement.lb211 |