BRCA2 translocates to the nucleus

Stable Identifier
R-HSA-9709273
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol, nucleoplasm
ReviewStatus
5/5
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BRCA2 translocates to the nucleus
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BRCA2 possesses two functional nuclear localization signals (NLSs) in its C-terminal region. NLS1 has been mapped to amino acid residues 3263-3269, while NLS2 has been mapped to residues 3381-3385 (Spain et al. 1999, Yano et al. 2000). A third putative NLS maps to residues 3311-3317, however it was shown to be nonfunctional (Spain et al. 1999, Yano et al. 2000). NLS1 is essential for localization of BRCA2 to the nucleus, while NLS2 is not essential.

Binding of BRCA2 to SEM1 (DSS1) is needed for the translocation of BRCA2 to the nucleus and nuclear retention. SEM1 prevents BRCA2 oligomerization, which leads to cytosolic retention (Lee et al. 2021). Binding of SEM1 to BRCA2 masks the nuclear export signal of BRCA2, resulting in nuclear retention of BRCA2 (Jeyasekharan et al. 2013).
Literature References
PubMed ID Title Journal Year
33978741 Cancer-causing BRCA2 missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance

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

Nucleic Acids Res 2021
10570174 Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations

Spain, BH, Larson, CJ, Shihabuddin, LS, Gage, FH, Verma, IM

Proc Natl Acad Sci U S A 1999
10733923 Nuclear localization signals of the BRCA2 protein

Yano, K, Morotomi, K, Saito, H, Kato, M, Matsuo, F, Miki, Y

Biochem Biophys Res Commun 2000
24013206 A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization

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

Nat Struct Mol Biol 2013
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Authored
Orlic-Milacic, M  (2020-12-11)
Reviewed
Liu, J  (2022-01-26)
Le, HP  (2022-01-26)
Heyer, WD  (2022-01-26)
Created
Orlic-Milacic, M  (2020-12-11)
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