Insights into DNA recombination from the structure of a RAD51–BRCA2 complex
| Autor: | Miyoung Lee, Thomas Lo, Ashok R. Venkitaraman, Shubha Anand, Luca Pellegrini, Tom L. Blundell, David S. Yu |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Repetitive Sequences Amino Acid Macromolecular Substances DNA repair Amino Acid Motifs Molecular Sequence Data genetic processes RAD51 Breast Neoplasms Biology Crystallography X-Ray Conserved sequence chemistry.chemical_compound Protein structure Recombinase Animals Humans Genetic Predisposition to Disease Amino Acid Sequence Peptide sequence Conserved Sequence BRCA2 Protein Recombination Genetic Genetics Binding Sites Multidisciplinary Protein Structure Tertiary DNA-Binding Proteins enzymes and coenzymes (carbohydrates) chemistry Mutation health occupations Rad51 Recombinase biological phenomena cell phenomena and immunity Homologous recombination Hydrophobic and Hydrophilic Interactions DNA Protein Binding |
| Zdroj: | Nature. 420:287-293 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature01230 |
| Popis: | The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility. |
| Databáze: | OpenAIRE |
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