BRCA1

breast cancer 1, early onset

Gene Information

Gene Symbol
BRCA1
Aliases
RNF53, BRCC1, PPP1R53, FANCS
HGNC ID
HGNC:1100
NCBI Gene ID
672
Ensembl Gene ID
ENSG00000012048
Gene Type
protein coding

Genomic Location

Chromosome
17
Assembly
GRCh38
Start Position
43,044,292
End Position
43,170,245
Number of Exons
23
Gene Length
125,954 bp

Overview

BRCA1 is crucial in cellular responses to DNA damage and may also be a transcriptional regulator. It interacts with WRN. Mutations in BRCA1 result in embryonic lethality in mice and humans. Mice hypomorphic for BRCA1 and heterozygous for TP53 have slower growth rates and display signs of premature ageing starting at about 8 months of age. Loss or haploid loss of CHEK2 also enables mice lacking BRCA1 to avoid embryonic lethality and display signs of premature ageing at about 18 months of age and develop multiple tumours later in life. In humans, some evidence suggests differences in BRCA1 genotype frequencies between centenarians and controls. BRCA1's role in cancer in humans is undisputed, and it is possible it also plays a role in ageing.

Research Papers

12 papers in databaseSearch for More Papers
#1
Score:
90%

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.

Nat Commun
2024
PMID: 38824133

Modification Effects

C-terminal TREX1 variants; aberrant mislocalization to nucleus, inhibition of homology-directed repair (HDR), and increased DNA damage vulnerability

Longevity Association

Premature senescence, early-onset breast cancer, and microvascular disease in humans; mechanism: genomic instability, DNA damage, and impaired DNA repair in Drosophila, mice, and humans

#2
Score:
90%

53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination.

Mol Cell
2020
PMID: 31653568

Modification Effects

53BP1 S25A mutation; altered interaction with PTIP, increased RIF1/shieldin activity, and disrupted RAD51 loading

Longevity Association

Premature aging in BRCA1-deficient mice; mechanism: homologous recombination insufficiency, genomic instability

#3
Score:
80%

Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes.

Nat Commun
2025
PMID: 40021682

Longevity Association

Reduced lifespan associated with loss-of-function variants in TET2, ATM, BRCA2, CKMT1B, BRCA1, ASXL1, and pathogenic missense variants in DNMT3A, SF3B1, TET2, PTEN, SOX21, TP53, SRSF2, RLIM; mechanism: oncogenic pathways and clonal hematopoiesis in humans

#4
Score:
80%

Conditional loss of Brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice.

EBioMedicine
2024
PMID: 39084071

Modification Effects

Conditional loss of Brca1 in oocytes; reduced ovarian reserve, impaired oocyte maturation

#5
Score:
80%

Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence.

Nat Commun
2015
PMID: 26106036

Modification Effects

BRCA1 haploinsufficiency; increased genomic instability, telomere erosion, and misregulation of SIRT1

Longevity Association

Premature senescence in human mammary epithelial cells; mechanism: pRb pathway activation, telomere shortening, and epigenetic changes

#6
Score:
80%

Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans.

Sci Transl Med
2013
PMID: 23408054

Modification Effects

BRCA1 deficiency or mutation; impaired ATM-mediated DNA double-strand break repair, reduced expression of BRCA1, MRE11, Rad51, and ATM

Longevity Association

Impaired reproductive capacity, reduced primordial follicle counts, and increased DNA double-strand breaks in mice and humans; mechanism: defective DNA repair efficiency

#7
Score:
80%

The burden of rare protein-truncating genetic variants on human lifespan.

Nat Aging
2022
PMID: 37117740

Modification Effects

Protein-truncating variants (PTVs) in genes BRCA1, BRCA2, ATM, and TET2; loss of function

Longevity Association

Association with human lifespan, particularly through cancer and clonal hematopoiesis mechanisms; modest overlap with common variant-based GWASs

#8
Score:
80%

The Histone Variant MacroH2A1 Is a BRCA1 Ubiquitin Ligase Substrate.

Cell Rep
2017
PMID: 28564596

Modification Effects

Ubiquitination of macroH2A1 at lysine 123; defective cellular senescence with ubiquitination-deficient macroH2A1 mutant

Longevity Association

Impaired cellular senescence in human fibroblasts; mechanism: macroH2A1 K123 ubiquitination

#9
Score:
80%

Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer.

Cancer
2012
PMID: 22139894

Modification Effects

BRCA2 mutations; altered DNA repair properties

Longevity Association

Improved overall survival in BRCA2-associated serous ovarian cancer; 100% 3-year survival rate, hazard ratio 0.20 compared to BRCA-negative patients

#10
Score:
80%

Better life expectancy in women with BRCA2 compared with BRCA1 mutations is attributable to lower frequency and later onset of ovarian cancer.

Cancer Epidemiol Biomarkers Prev
2008
PMID: 18559571

Modification Effects

BRCA1 and BRCA2 mutations; altered cancer risk and incidence

Longevity Association

Reduced life expectancy in BRCA1 carriers compared to BRCA2; mechanism: increased death rate from ovarian cancer

#11
Score:
80%

A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment.

Breast Cancer Res
2004
PMID: 14680495

Modification Effects

BRCA1/BRCA2 germline mutations; altered breast cancer prognosis and survival

Longevity Association

Reduced survival in BRCA1 mutation carriers (62% at 10 years vs 86% without mutation); improved prognosis with adjuvant chemotherapy; human study, specifically Ashkenazi Jewish women

#12
Score:
60%

Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations.

Nat Aging
2021
PMID: 35187501

Longevity Association

Accelerated aging in human mammary epithelia; hallmarks include loss of lineage fidelity, increased luminal epithelial cells with myoepithelial markers, and decreased myoepithelial cells in BRCA1 or BRCA2 mutation carriers

Return to Knowledge Base