Crystal structure of a Rad51 filament
Abstract
Rad51, the major eukaryotic homologous recombinase, is important for the repair of DNA damage and the maintenance of genomic diversity and stability. The active form of this DNA-dependent ATPase is a helical filament within which the search for homology and strand exchange occurs. Here we present the crystal structure of a Saccharomyces cerevisiae Rad51 filament formed by a gain-of-function mutant. This filament has a longer pitch than that seen in crystals of Rad51's prokaryotic homolog RecA, and places the ATPase site directly at a new interface between protomers. Although the filament exhibits approximate six-fold symmetry, alternate protein-protein interfaces are slightly different, implying that the functional unit of Rad51 within the filament may be a dimer. Additionally, we show that mutation of His352, which lies at this new interface, markedly disrupts DNA binding.
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The model of the trimeric Rad55-Rad57-Rad51 complex, in combination with the known Rad51 filament structure, suggests that Rad55-Rad57 binds at the 5' end of the Rad51 filament where it could promote growth of the Rad51 filament in a directional manner.
“We generated a model of the trimeric Rad55–Rad57–Rad51 complex, which in combination with the known Rad51 filament structure (37), suggests that Rad55–Rad57 binds at the 5’ end of the Rad51 filament where it could promote growth of the Rad51 filament in a directional manner (Fig. 5B and fig. S18).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [37]
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- Authors
- Conway, A. B., Lynch, T. W., Zhang, Y., Fortin, G. S., Fung, C. W., Symington, L. S., & Rice, P. A.
- Affiliations
- University of Chicago (US)
- Fox Chase Cancer Center (US)
- Columbia University (US)
- Corresponding author
- Rice, Phoebe A
- Venue
- Nature Structural & Molecular Biology
- Published
- 2004-07-04
- Volume
- 11
- Issue
- 8
- Pages
- 791-796
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2066616729
- Cited by
- 310
- References
- 40
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 15 · 2017: 8 · 2016: 25 · 2015: 7 · 2014: 16 · 2013: 14 · 2012: 16
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA09594, T32 CA 09503, T32CA009503, T32CA009594)
- National Institute of General Medical Sciences (R01GM058827, R01GM054099, GM 54099, T32GM008720, GM058827)
- National Center for Research Resources (RR07 707)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- RAD51, homologous recombination, DNA-dependent ATPase, helical filaments, RecA, DNA strand exchange, DNA repair, genome stability, protein-protein interfaces, ATPase site, hexagonal symmetry, dimers, DNA binding, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, Adenosine Triphosphate, DNA, DNA Damage, DNA-Binding Proteins, Histidine, Hydrogen-Ion Concentration, Hydrolysis, Models, Molecular, Mutation, Phosphorylation, Protein Binding, Protein Conformation, Rec A Recombinases, Saccharomyces cerevisiae, Time Factors, Tyrosine, Crystallography, X-Ray, Saccharomyces cerevisiae Proteins, Rad51 Recombinase
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