BRIP1

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.

This protein also appears to be important in ovarian cancer where it seems to act as a tumor suppressor.{{cite journal | vauthors = Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, Sigurdsson A, Jonasdottir A, Besenbacher S, Lundin P, Stacey SN, Gudmundsson J, Magnusson OT, le Roux L, Orlygsdottir G, Helgadottir HT, Johannsdottir H, Gylfason A, Tryggvadottir L, Jonasson JG, de Juan A, Ortega E, Ramon-Cajal JM, García-Prats MD, Mayordomo C, Panadero A, Rivera F, Aben KK, van Altena AM, Massuger LF, Aavikko M, Kujala PM, Staff S, Aaltonen LA, Olafsdottir K, Bjornsson J, Kong A, Salvarsdottir A, Saemundsson H, Olafsson K, Benediktsdottir KR, Gulcher J, Masson G, Kiemeney LA, Mayordomo JI, Thorsteinsdottir U, Stefansson K | display-authors = 6 | title = Mutations in BRIP1 confer high risk of ovarian cancer | journal = Nature Genetics | volume = 43 | issue = 11 | pages = 1104–1107 | date = October 2011 | pmid = 21964575 | doi = 10.1038/ng.955 | hdl-access = free | s2cid = 24535565 | hdl = 2336/228034 }} Mutations in BRIP1 are associated with a 10-15% risk of ovarian cancer.{{cite journal | vauthors = Ring KL, Garcia C, Thomas MH, Modesitt SC | title = Current and future role of genetic screening in gynecologic malignancies | journal = American Journal of Obstetrics and Gynecology | volume = 217 | issue = 5 | pages = 512–521 | date = November 2017 | pmid = 28411145 | doi = 10.1016/j.ajog.2017.04.011 | s2cid = 29024566 }}

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.{{cite journal | vauthors = Mani C, Acharya G, Kshirsagar S, Vijayan M, Khan H, Reddy PH, Palle K | title = A Novel Role for BRIP1/FANCJ in Neuronal Cells Health and in Resolving Oxidative Stress-Induced DNA Lesions | journal = Journal of Alzheimer's Disease | volume = 85 | issue = 1 | pages = 207–221 | date = 2022 | pmid = 34776453 | doi = 10.3233/JAD-215305 | s2cid = 244078679 }} A deficiency of BRIP1 causes increased DNA damage, mitochondrial abnormalities and neuronal cell death.

BRIP1 protein is a DNA helicase that is employed in homologous recombinational repair, and in the response of the cell to DNA replication stress.{{cite journal | vauthors = Sun X, Brieño-Enríquez MA, Cornelius A, Modzelewski AJ, Maley TT, Campbell-Peterson KM, Holloway JK, Cohen PE | display-authors = 6 | title = FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice | journal = Chromosoma | volume = 125 | issue = 2 | pages = 237–252 | date = June 2016 | pmid = 26490168 | pmc = 5415080 | doi = 10.1007/s00412-015-0549-2 }} In part, BRIP1 carries out its function through interaction with other key DNA repair proteins, specifically MLH1, BRCA1 and BLM. This group of proteins helps to ensuring genome stability, and in particular repairs DNA double-strand breaks during prophase 1 of 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.{{cite journal |vauthors=Horan TS, Ascenção CF, Mellor CA, Wang M, Smolka MB, Cohen PE |title=The DNA helicase FANCJ (BRIP1) functions in Double Strand Break repair processing, but not crossover formation during Prophase I of meiosis in male mice |journal=bioRxiv |volume= |issue= |pages= |date=October 2023 |pmid=37873301 |pmc=10592954 |doi=10.1101/2023.10.06.561296 |url=}} 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.

BRIP1 has been shown to interact with BRCA1.{{cite journal | vauthors = Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G | title = Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains | journal = Structure | volume = 12 | issue = 7 | pages = 1137–1146 | date = July 2004 | pmid = 15242590 | pmc = 3652423 | doi = 10.1016/j.str.2004.06.002 }}{{cite journal | vauthors = Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP | title = Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure | journal = Genes & Development | volume = 16 | issue = 5 | pages = 583–593 | date = March 2002 | pmid = 11877378 | pmc = 155350 | doi = 10.1101/gad.959202 }}{{cite journal | vauthors = Yu X, Chini CC, He M, Mer G, Chen J | title = The BRCT domain is a phospho-protein binding domain | journal = Science | volume = 302 | issue = 5645 | pages = 639–642 | date = October 2003 | pmid = 14576433 | doi = 10.1126/science.1088753 | s2cid = 29407635 | bibcode = 2003Sci...302..639Y }}{{cite journal | vauthors = Rodriguez M, Yu X, Chen J, Songyang Z | title = Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 52914–52918 | date = December 2003 | pmid = 14578343 | doi = 10.1074/jbc.C300407200 | doi-access = free }}{{cite journal | vauthors = Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ | title = Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 6 | pages = 512–518 | date = June 2004 | pmid = 15133502 | doi = 10.1038/nsmb775 | s2cid = 7354915 }}

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• {{cite journal | vauthors = Kobayashi A, Yamagiwa H, Hoshino H, Muto A, Sato K, Morita M, Hayashi N, Yamamoto M, Igarashi K | display-authors = 6 | title = A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain | journal = Molecular and Cellular Biology | volume = 20 | issue = 5 | pages = 1733–1746 | date = March 2000 | pmid = 10669750 | pmc = 85356 | doi = 10.1128/MCB.20.5.1733-1746.2000 }}
• {{cite journal | vauthors = Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP | title = Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure | journal = Genes & Development | volume = 16 | issue = 5 | pages = 583–593 | date = March 2002 | pmid = 11877378 | pmc = 155350 | doi = 10.1101/gad.959202 }}
• {{cite journal | vauthors = Luo L, Lei H, Du Q, von Wachenfeldt A, Kockum I, Luthman H, Vorechovsky I, Lindblom A | display-authors = 6 | title = No mutations in the BACH1 gene in BRCA1 and BRCA2 negative breast-cancer families linked to 17q22 | journal = International Journal of Cancer | volume = 98 | issue = 4 | pages = 638–639 | date = April 2002 | pmid = 11920628 | doi = 10.1002/ijc.10214 | s2cid = 31182390 | doi-access = free }}
• {{cite journal | vauthors = Karppinen SM, Vuosku J, Heikkinen K, Allinen M, Winqvist R | title = No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families | journal = European Journal of Cancer | volume = 39 | issue = 3 | pages = 366–371 | date = February 2003 | pmid = 12565990 | doi = 10.1016/S0959-8049(02)00498-7 }}
• {{cite journal | vauthors = Rutter JL, Smith AM, Dávila MR, Sigurdson AJ, Giusti RM, Pineda MA, Doody MM, Tucker MA, Greene MH, Zhang J, Struewing JP | display-authors = 6 | title = 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 | journal = Human Mutation | volume = 22 | issue = 2 | pages = 121–128 | date = August 2003 | pmid = 12872252 | doi = 10.1002/humu.10238 | s2cid = 36167584 }}
• {{cite journal | vauthors = Suzuki H, Tashiro S, Sun J, Doi H, Satomi S, Igarashi K | title = Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene | journal = The Journal of Biological Chemistry | volume = 278 | issue = 49 | pages = 49246–49253 | date = December 2003 | pmid = 14504288 | doi = 10.1074/jbc.M306764200 | doi-access = free }}
• {{cite journal | vauthors = Yu X, Chini CC, He M, Mer G, Chen J | title = The BRCT domain is a phospho-protein binding domain | journal = Science | volume = 302 | issue = 5645 | pages = 639–642 | date = October 2003 | pmid = 14576433 | doi = 10.1126/science.1088753 | s2cid = 29407635 | bibcode = 2003Sci...302..639Y }}
• {{cite journal | vauthors = Rodriguez M, Yu X, Chen J, Songyang Z | title = Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 52914–52918 | date = December 2003 | pmid = 14578343 | doi = 10.1074/jbc.C300407200 | doi-access = free }}
• {{cite journal | vauthors = Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM | title = The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 8 | pages = 2357–2362 | date = February 2004 | pmid = 14983014 | pmc = 356955 | doi = 10.1073/pnas.0308717101 | doi-access = free | bibcode = 2004PNAS..101.2357C }}
• {{cite journal | vauthors = Shiozaki EN, Gu L, Yan N, Shi Y | title = Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling | journal = Molecular Cell | volume = 14 | issue = 3 | pages = 405–412 | date = May 2004 | pmid = 15125843 | doi = 10.1016/S1097-2765(04)00238-2 | doi-access = free }}
• {{cite journal | vauthors = Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ | title = Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 6 | pages = 512–518 | date = June 2004 | pmid = 15133502 | doi = 10.1038/nsmb775 | s2cid = 7354915 }}
• {{cite journal | vauthors = Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G | title = Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains | journal = Structure | volume = 12 | issue = 7 | pages = 1137–1146 | date = July 2004 | pmid = 15242590 | pmc = 3652423 | doi = 10.1016/j.str.2004.06.002 }}
• {{cite journal | vauthors = Gupta R, Sharma S, Sommers JA, Jin Z, Cantor SB, Brosh RM | title = Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer | journal = The Journal of Biological Chemistry | volume = 280 | issue = 27 | pages = 25450–25460 | date = July 2005 | pmid = 15878853 | doi = 10.1074/jbc.M501995200 | doi-access = free }}

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{{DNA repair}}

• {{UCSC gene info|BACH1}}
• {{UCSC gene info|BRIP1}}

Category:Helicases

Category:Human proteins