Fanconi anemia group J protein is a
protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1)
gene.[5][6][7]
Function
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 suppressing
oxidative stress,
excitotoxicity induced
DNA damage, and in protecting the integrity of
mitochondria.[10] A deficiency of BRIP1 causes increased DNA damage, mitochondrial abnormalities and
neuronal cell death.
DNA repair
BRIP1 protein is a DNA
helicase that is employed in
homologous recombinational repair, and in the response of the cell to
DNA replication stress.[11] In part, BRIP1 carries out its function through interaction with other key DNA repair proteins, specifically
MLH1,
BRCA1 and
BLM.[11] This group of proteins helps to ensuring genome stability, and in particular repairs DNA double-strand breaks during prophase 1 of
meiosis.
Meiosis
During
prophase I of
meiosis in male mice, BRIP1 functions in the
repair of DNA double-strand breaks, but does not appear to have a role in the formation of
chromosomal crossovers.[12] BRIP1 co-localizes with
TOPBP1 scaffold protein and the
BRCA1 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]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Menichini P, Linial M (November 2001). "SUVi and BACH1: a new subfamily of mammalian helicases?". Mutation Research. 487 (1–2): 67–71.
doi:
10.1016/s0921-8777(01)00104-5.
PMID11595410.
^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.