Biomaterial Database

BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. 1999

J J Chen, and D Silver, and S Cantor, and D M Livingston, and R Scully

The Dana-Faber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle.

UI	MeSH Term	Description	Entries
D009363	Neoplasm Proteins	Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.	Proteins, Neoplasm
D011995	Recombination, Genetic	Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.	Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D051135	Rad51 Recombinase	A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.	RAD51 Protein,Recombinase, Rad51
D019398	Genes, BRCA1	A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.	BRCA1 Gene,BRCA1 Genes,Gene, BRCA1