The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure
Abstract
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a ∼90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT) 9 , (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.
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Citations
Cites
Biallelic Inactivation of BRCA2 in Fanconi Anemia
Howlett, N. G., Taniguchi, T., Olson, S., Cox, B., Waisfisz, Q., de Die-Smulders, C., Persky, N., Grompe, M., Joenje, H., Pals, G., et al. (2002) · Science · doi:10.1126/science.1073834 · Cited by 1,149
Sung, P. (1997) · Genes & Development · doi:10.1101/gad.11.9.1111 · Cited by 540
Cited by
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577
Regulation of DNA double-strand break repair pathway choice
Shrivastav, M., De Haro, L. P., & Nickoloff, J. A. (2008) · Cell Research · doi:10.1038/cr.2007.111 · Cited by 1,329
Resistance to therapy caused by intragenic deletion in BRCA2
Edwards, S. L., Brough, R., Lord, C. J., Natrajan, R., Vatcheva, R., Levine, D. A., Boyd, J., Reis-Filho, J. S., & Ashworth, A. (2008) · Nature · doi:10.1038/nature06548 · Cited by 1,011
Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.022 · Cited by 861
Metadata
- Authors
- Yang, H., Jeffrey, P. D., Miller, J., Kinnucan, E., Sun, Y., Thomä, N. H., Zheng, N., Chen, P.-L., Lee, W.-H., & Pavletich, N. P.
- Venue
- Science
- Published
- 2002-09-13
- Volume
- 297
- Issue
- 5588
- Pages
- 1837-1848
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1961774825
- Cited by
- 705
- References
- 2
- FWCI
- 14.79
- Type
- journal article
- Language
- en
- Open access
- closed
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- Yang, H., Jeffrey, P. D., Miller, J., Kinnucan, E., Sun, Y., Thomä, N. H., Zheng, N., Chen, P.-L., Lee, W.-H., & Pavletich, N. P. (2002). BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure. Science. https://doi.org/10.1126/science.297.5588.1837
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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