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.[7]
This protein also appears to be important in ovarian cancer where it seems to act as a tumor suppressor.[8] Mutations in BRIP1 are associated with a 10-15% risk of ovarian cancer.[9]
BRIP1 appears to have an important role in neuronal cells by suppressingoxidative stress,excitotoxicity inducedDNA damage, and in protecting the integrity ofmitochondria.[10] A deficiency of BRIP1 causes increased DNA damage, mitochondrial abnormalities andneuronal cell death.
BRIP1 protein is a DNAhelicase that is employed inhomologous recombinational repair, and in the response of the cell toDNA replication stress.[11] In part, BRIP1 carries out its function through interaction with other key DNA repair proteins, specificallyMLH1,BRCA1 andBLM.[11] This group of proteins helps to ensuring genome stability, and in particular repairs DNA double-strand breaks during prophase 1 ofmeiosis.
Duringprophase I ofmeiosis in male mice, BRIP1 functions in therepair of DNA double-strand breaks, but does not appear to have a role in the formation ofchromosomal crossovers.[12] BRIP1 co-localizes withTOPBP1 scaffold protein and theBRCA1 repair protein along chromosome cores starting early in meiotic prophase I forming discrete foci, and is also densely localized to the axes of unsynapsed chromosomes during the late zygonema (zygotene) stage of meiosis.[12]
^Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, Sigurdsson A, Jonasdottir A, et al. (October 2011). "Mutations in BRIP1 confer high risk of ovarian cancer".Nature Genetics.43 (11):1104–1107.doi:10.1038/ng.955.hdl:2336/228034.PMID21964575.S2CID24535565.
^Ring KL, Garcia C, Thomas MH, Modesitt SC (November 2017). "Current and future role of genetic screening in gynecologic malignancies".American Journal of Obstetrics and Gynecology.217 (5):512–521.doi:10.1016/j.ajog.2017.04.011.PMID28411145.S2CID29024566.
^Mani C, Acharya G, Kshirsagar S, Vijayan M, Khan H, Reddy PH, Palle K (2022). "A Novel Role for BRIP1/FANCJ in Neuronal Cells Health and in Resolving Oxidative Stress-Induced DNA Lesions".Journal of Alzheimer's Disease.85 (1):207–221.doi:10.3233/JAD-215305.PMID34776453.S2CID244078679.
Karppinen SM, Vuosku J, Heikkinen K, Allinen M, Winqvist R (February 2003). "No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families".European Journal of Cancer.39 (3):366–371.doi:10.1016/S0959-8049(02)00498-7.PMID12565990.
Rutter JL, Smith AM, Dávila MR, Sigurdson AJ, Giusti RM, Pineda MA, et al. (August 2003). "Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals".Human Mutation.22 (2):121–128.doi:10.1002/humu.10238.PMID12872252.S2CID36167584.
