Brca1

Symbol: Brca1
Name: Breast cancer 1
Entrez gene ID: 12189
Ensembl gene ID: ENSMUSG00000017146
Species: Mouse (Taxid: 10090)

Functional description:
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (By similarity). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. [UniProt]

Observation:

Deletion of Brca1 causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature aging in adults [12533509]. Brca1 heterozygous appear to have shortened lifespan with 70% of tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these animals. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence to ovarian tumors, but not lymphoma, when compared with Brca1(+/+) mice [17420720].



Interventions:
  • Brca1 deletion

  • Assays: Organismal Lifespan

    Classification:
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Cancer-Related
  • Tumor-Suppressor


  • References:
  • 17420720: Brca1 heterozygous mice have shortened life span and are prone to ovarian tumorigenesis with haploinsufficiency upon ionizing irradiation.
  • 12533509: Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • BRCA1 (9606)
  • BRCA1 (9598)
  • BRCA1 (9615)
  • BRCA1 (9913)
  • Brca1 (10090)
  • Brca1 (10116)
  • BRCA1 (9031)



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