BRCA2 binds SEM1 (DSS1)

Stable Identifier
Reaction [binding]
Homo sapiens
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DSS1 is a critical and positive effector of BRCA2 function (Gudmundsdottir et al. 2004), which binds through the BRCA2 helical domain, OB1 and OB2 folds (Marston et al. 1999, Yang et al. 2002). Defective binding of DSS1 leads to reduced homologous recombination repair (HRR) activity of BRCA2 mutant constructs in mice (K2630A and K2630D) (Siaud et al. 2011). BRCA2 D2723H mutation is cancer-predisposing and leads to cytoplasmic mislocalization of BRCA2 due to wrongly exposed nuclear export signals as a consequence of defective DSS1 binding (Jeyasekhran et al. 2013). DSS1 controls the oligomeric state of BRCA2 and stabilizes the monomeric form of BRCA2 (Le et al. 2020). Defective DSS1 binding leads to intracellular oligomerization and cytosolic mislocalization (Le et al. 2020, Lee et al. 2021, reviewed in Le et al. 2021).
Literature References
PubMed ID Title Journal Year
33978741 Cancer-causing BRCA2 missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance

Shorthouse, D, Hall, BA, Venkitaraman, AR, Mahen, R, Lee, M

Nucleic Acids Res 2021
10373512 Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals

Richards, WJ, Marston, NJ, Hughes, D, Ashworth, A, Marshall, CJ, Bertwistle, D

Mol Cell Biol 1999
15359272 DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells

Ashworth, A, Tutt, AN, Gudmundsdottir, K, Witt, E, Lord, CJ

EMBO Rep 2004
12228710 BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure

Zheng, N, Chen, PL, Jeffrey, PD, Thomä, NH, Sun, Y, Pavletich, NP, Yang, H, Lee, WH, Kinnucan, E, Miller, J

Science 2002
22194698 Plasticity of BRCA2 function in homologous recombination: genetic interactions of the PALB2 and DNA binding domains

Siaud, N, Christ, N, Jasin, M, Xia, B, Barbera, MA, Egashira, A, Schlacher, K, Lam, I

PLoS Genet 2011
34440403 Guardians of the Genome: BRCA2 and Its Partners

Heyer, WD, Le, HP, Liu, J

Genes (Basel) 2021
24013206 A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization

Liu, Y, Rajendra, E, Jonsdottir, AB, Ayoub, N, Sato, K, Savill, J, Venkitaraman, AR, Lee, M, Sundaramoorthy, E, Pisupati, V, Kaminski, CF, Schlachter, S, Hattori, H, Jeyasekharan, AD, Ofir-Rosenfeld, Y

Nat Struct Mol Biol 2013
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