motifs/domains
| N-terminal PALB2 (partner and localizer of BRCA2)-binding domain  |
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eight internal repeats (BRC 1-8 domains), with histone acetyltransferase intrinsic activity (HAT) which map to the N terminal region (truncated BRCA2 mutants are cytoplasmic and non functional), mediate the interaction of BRCA2 with RAD51, and essential for homology-directed repair (HDR) , and, Valine 1532 of BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51 |
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a specific DMC1 interacting region in B2-6.5, (BRCA2 2340-2472) |
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two C terminal nuclear localization signals (NLS) |
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for binding ssDNA and dsDNA |
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a functional nuclear export sequence (NES1)(disruption of the NES function results in deregulation of BRCA2 export, which ultimately leads to centrosome disorder) |
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C-terminal DNA-binding domain (DBD), with unique structural features and C-terminal domain of BRCA2 (BRCA2CTD) interacted with TP53 TAD1 and TAD2, and including C-terminal RAD51 interaction domain (CTRD) |
| basic FUNCTION
| histone acetyltransferase intrinsic activity (HAT) |
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involved in cell cycle control and in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair |
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is required for cellular proliferation during embryogenesis |
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involved in transcription-associated recombination (TAR) |
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playing an early role in homologous double-strand breaks repair pathway choice |
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involved in embryonic cellular proliferation |
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universal regulator of RAD51/DMC1 recombinase actions |
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as in mitotic cells, it is likely that BRCA2 may participate in nucleoprotein filament formation leading to subsequent repair |
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essential for the ability to survive DNA damage and efficient homology-directed repair, presumably in conjunction with the RAD51 recombinase |
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regulates both the intracellular localization and DNA-binding ability of RAD51 |
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promotes homologous recombination comprising one major pathway of DNA double-strand break repair |
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may regulate the fidelity of late stages in cytokinesis and may have a role in normal organization of myosin II in the contractile ring during cell division |
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has a role in the cellular response to blocked DNA replication |
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a central role in recombination, assembling onto single-stranded DNA (ssDNA) as a nucleoprotein filament and catalysing the invasion and exchange of homologous DNA sequences |
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plays significant roles in DNA double-strand break repair |
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the BRC repeats of BRCA2 regulate DNA-binding selectivity by modulating RAD51-DNA interaction |
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may limit the metastatic potential of neoplastic cells by down-regulating MMP9 production through inhibition of PI3-kinase/AKT and activation of MAPK/ERK, effectively hindering cancer cell migration and invasion |
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plays an essential role in the chromatin assembly of RAD51 during homologous recombination repair (HRR) |
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PALB2 can work in concert with a BRCA2 construct to further promote D-loop formation |
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may act as a molecular chaperone for RAD51 loading |
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key mediator of homologous recombination |
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augments the functions of RAD51 that are essential for recombinational repair of DNA breaks |
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associates with telomeres during the S and G2 phases of the cell cycle and facilitates the loading of RAD51 onto telomeres |
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besides its role in DNA damage repair, also plays an important role in cytokinesis, transcription regulation, and cancer cell proliferation |
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prevents rather than repairs nucleolytic lesions at stalled replication forks to maintain genomic integrity and hence likely suppresses tumorigenesis through this replication-specific function |
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critical role for BRCA2 in maintaining genomic stability, and likely suppressing tumorigenesis, independent of homology-directed repair |
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HDR-independent role of BRCA2 in preventing the degradation of stalled replication forks and the resultant chromosome rearrangements has important implications for therapy |
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BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage |
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cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling its localization |
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cellular levels of BRCA2 and RAD51 are mutually dependent on each other, and that low levels of these proteins provide selective pressure for reduction of TP53, which permits cell growth |
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R-loops are frequently formed in cells and BRCA2 is required for their processing |
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has a key role in the repair of DNA double-strand breaks and interstrand cross-links by RAD51-mediated homologous recombination |
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has dual functionality promoting not only DNA repair but also preventing DNA lesions at stalled forks |
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by targeting RPA1 and mimicking DNA, SHFM1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression |
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likely unique and specialized functions for the BRC motifs of BRCA2 in promoting homologous recombination in meiotic and mitotic cells |
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FANCA, FANCF, FANCL, FANCD2, BRCA1, and BRCA2, are required for mitophagy |
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multifunctional tumor suppressor involved in homologous recombination (HR), mitotic checkpoint regulation, and telomere homeostasis |
