BRCA2

Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, Dec 2008]

BRCA2, DNA Repair Associated

Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180).

Brain development Source: Ensembl
Cell aging Source: Ensembl
Centrosome duplication Source: UniProtKB
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: Ensembl
Double-strand break repair Source: UniProtKB
Double-strand break repair via homologous recombination Source: UniProtKB
Establishment of protein localization to telomere Source: BHF-UCL
Female gonad development Source: Ensembl
Hemopoiesis Source: Ensembl
Histone H3 acetylation Source: UniProtKB
Histone H4 acetylation Source: UniProtKB
Inner cell mass cell proliferation Source: Ensembl
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
Male meiosis I Source: Ensembl
Mitotic recombination-dependent replication fork processing Source: BHF-UCL
Negative regulation of mammary gland epithelial cell proliferation Source: UniProtKB
Nucleotide-excision repair Source: UniProtKB
Oocyte maturation Source: Ensembl
Positive regulation of mitotic cell cycle Source: Ensembl
Positive regulation of transcription, DNA-templated Source: UniProtKB
Regulation of cytokinesis Source: Ensembl
Regulation of transcription, DNA-templated Source: GO_Central
Replication fork protection Source: Ensembl
Response to gamma radiation Source: Ensembl
Response to UV-C Source: Ensembl
Response to X-ray Source: Ensembl
Spermatogenesis Source: Ensembl
Telomere maintenance via recombination Source: Ensembl

Centrosome; Nucleus. Colocalizes with ERCC5/XPG to nuclear foci following DNA replication stress.

Breast cancer (BC): A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Pancreatic cancer 2 (PNCA2): A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
Breast-ovarian cancer, familial, 2 (BROVCA2): A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
Fanconi anemia complementation group D1 (FANCD1): A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Glioma 3 (GLM3): Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.

Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination-dependent repair during S phase and G2 by inhibiting RAD51 binding.
Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation.