BRIP1 GENE - BRCA1 (Breast Cancer 1) Interacting Protein C-terminal (BRIP1) Gene

BRIP1, also known as BACH1 (BRCA1-associated C-terminal Helicase-1) or FANCJ (Fanconi Anemia Complementation Group J), is a member of the helicase family [1]. Helicases are necessary for numerous processes involving DNA [2].The role of DNA helicases has been directly linked to diseases in humans [3].

The BRIP1 DNA helicase binds with BRCA1 to form a complex which checks for DNA damage. These checks allow for the repair of DNA breaks, control gene stability and help to prevent tumors [1,3]. BACH1 (BRIP1) mutations have been shown to prevent DNA repair by inhibiting helicase activity [3,4] . DNA repair is necessary to regulate normal cell growth [1]. These disruptions are linked to several types of cancer including breast, ovarian and cervical [1].

Mutations in BRIP1 also lead to the development of Fanconi Anemia (FA). FA is an instability in genes which results in developmental abnormalities, bone marrow failure, solid tumors and a predisposition to cancer [1].

Changes in BRIP1 gene significantly increase a woman’s chances of developing ovarian cancer. The risk of female breast cancer increases by 12.5% over a lifetime. However the mutation causes no known cancer risks in men [5].

     Covered on Genetics Home Reference: Fanconi anemiaovarian cancerbreast cancerFrom NCBI Gene: Tracheoesophageal fistulaFanconi anemia, complementation group JFamilial cancer of breastFrom UniProt: 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. [MIM:114480] Fanconi anemia complementation group J (FANCJ): 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. [MIM:609054]

     From NCBI Gene: The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008] From UniProt: DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1.

The following transcription factors affect gene expression:

• C/EBPalpha
• Meis-1
• MRF-2
• CUTL1
• NF-kappaB1
• NF-kappaB2
• NF-kappaB

Tissue specificity:

Ubiquitously expressed, with highest levels in testis.

Cofactor:

Binds 1 [4Fe-4S] cluster.

Molecular Function:

• Dna Binding
• Structural Constituent Of Ribosome
• Atp-Dependent Dna Helicase Activity
• Atp Binding
• Metal Ion Binding
• 4 Iron, 4 Sulfur Cluster Binding

Biological Processes:

• Dna Damage Checkpoint
• Dna Synthesis Involved In Dna Repair
• Strand Displacement
• Dna Replication
• Double-Strand Break Repair
• Regulation Of Transcription From Rna Polymerase Ii Promoter
• Translation
• Negative Regulation Of Cell Proliferation
• Ribosome Biogenesis
• Mitochondrial Translational Elongation
• Mitochondrial Translational Termination
• Cellular Response To Vitamin
• Regulation Of Signal Transduction By P53 Class Mediator