BRCA1, breast cancer 1, early onset, BRCAI, BRCC1, BROVCA1, IRIS, PNCA4, PPP1R53, PSCP, RNF53, FANCS, breast cancer 1, DNA repair associated, BRCA1 DNA repair associated, Genes
• tubulin binding • metal ion binding • enzyme binding • zinc ion binding • damaged DNA binding • GO:0001948, GO:0016582 Ikatan protein plasma • GO:0001105 transcription coactivator activity • androgen receptor binding • RNA binding • ubiquitin protein ligase binding • GO:0050372 ubiquitin-protein transferase activity • DNA binding • transferase activity • RNA polymerase binding • pengikatan protein identik
Komponen seluler
• BRCA1-BARD1 complex • condensed nuclear chromosome • BRCA1-A complex • ubiquitin ligase complex • Membran sel • nucleoplasm • condensed chromosome • sitoplasma • kromosom • Inti sel • lateral element • GO:0009327 protein-containing complex • ribonucleoprotein complex
Proses biologis
• response to ionizing radiation • centrosome cycle • chromosome segregation • protein K6-linked ubiquitination • intrinsic apoptotic signaling pathway in response to DNA damage • Siklus sel • double-strand break repair via nonhomologous end joining • GO:0097285 Apoptosis • regulation of apoptotic process • regulation of gene expression by genetic imprinting • GO:0009373 regulation of transcription, DNA-templated • negative regulation of fatty acid biosynthetic process • transcription, DNA-templated • regulation of transcription by RNA polymerase III • fatty acid biosynthetic process • regulation of DNA methylation • negative regulation of intracellular estrogen receptor signaling pathway • protein autoubiquitination • positive regulation of histone H3-K9 methylation • DNA recombination • positive regulation of angiogenesis • response to estrogen • cellular response to indole-3-methanol • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors • GO:0045996 negative regulation of transcription, DNA-templated • positive regulation of protein ubiquitination • androgen receptor signaling pathway • negative regulation of centriole replication • postreplication repair • metabolisme lipid • cellular response to tumor necrosis factor • GO:1900404 positive regulation of DNA repair • Metabolisme asam lemak • GO:1901313 positive regulation of gene expression • negative regulation of histone H3-K4 methylation • regulation of cell population proliferation • negative regulation of reactive oxygen species metabolic process • positive regulation of vascular endothelial growth factor production • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • positive regulation of histone H4-K20 methylation • DNA double-strand break processing • double-strand break repair via homologous recombination • negative regulation of histone acetylation • protein ubiquitination • positive regulation of histone H3-K4 methylation • GO:0100026 Reparasi DNA • double-strand break repair • positive regulation of histone acetylation • dosage compensation by inactivation of X chromosome • negative regulation of histone H3-K9 methylation • positive regulation of histone H3-K9 acetylation • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • chordate embryonic development • positive regulation of histone H4-K16 acetylation • cellular response to DNA damage stimulus • protein deubiquitination • Replikasi DNA • mitotic G2/M transition checkpoint • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • negative regulation of G0 to G1 transition • transcription by RNA polymerase II • mitotic G2 DNA damage checkpoint signaling • regulation of signal transduction by p53 class mediator
Breast cancer type 1 susceptibility protein adalah protein yang pada manusia dikodekan oleh gen BRCA1.BRCA1 adalah gen penekan tumor (tumor supressor) pada manusia dan bertanggung jawab untuk memperbaiki kerusakan DNA.[4][5] Ortolog dari gen ini umum ditemukan pada spesies vertebrata lain selain manusia, sedangkan genom invertebrata mengkodekan gen terkait yang berkerabat jauh.[6]
BRCA1 dan BRCA2 adalah protein yang tidak saling berhubungan,[7] tetapi keduanya biasanya diekspresikan dalam sel payudara dan jaringan lain, di mana mereka membantu memperbaiki DNA yang rusak, atau menghancurkan sel jika DNA tidak dapat diperbaiki.[8][4] Keduanya terlibat dalam perbaikan kerusakan kromosom dengan peran penting dalam perbaikan kerusakan untai ganda DNA.[9][4]
Jika BRCA1 atau BRCA2 itu sendiri rusak akibat mutasi BRCA, maka DNA yang rusak tidak dapat diperbaiki dengan baik, dan hal ini meningkatkan risiko terjadinya kanker payudara.[8][9] Alel dominan memiliki fungsi penekan tumor yang normal, sedangkan mutasi penetrasi tinggi pada gen-gen ini menyebabkan hilangnya fungsi penekan tumor yang berkorelasi dengan peningkatan risiko kanker payudara.[10]
BRCA1 berasosiasi dengan protein penekan tumor lainnya, protein sensor kerusakan DNA, dan transduser sinyal untuk membentuk kompleks protein multi-subunit besar yang dikenal sebagai kompleks pengawasan genom yang terasosiasi dengan BRCA1 (BRCA1-associated genome surveillance complex, BASC).[11] Protein BRCA1 berasosiasi dengan RNA polimerase II, dan melalui domain C-terminal, juga berinteraksi dengan kompleks histone deacetylase.[9] Dengan demikian, protein ini berperan dalam transkripsi, dan perbaikan DNA dari kerusakan DNA untai ganda ubiquitinasi, regulasi transkripsi, serta fungsi lainnya.[12]
Penemuan
Bukti pertama keberadaan gen yang mengkode enzim perbaikan DNA yang terlibat dalam risiko terjadinya kanker payudara dikemukakan oleh laboratorium Mary-Claire King di UC Berkeley pada tahun 1990.[13] Empat tahun kemudian, setelah terjadi perlombaan internasional untuk menemukannya,[14] gen tersebut dikloning pada tahun 1994 oleh para ilmuwan di University of Utah, National Institute of Environmental Health Sciences (NIEHS), dan Myriad Genetics.[15]
Lokasi gen
Gen BRCA1 manusia terletak pada lengan panjang (q) kromosom 17 di wilayah 2 pita 1, dari pasangan basa 41.196.312 hingga pasangan basa 41.277.500 (Build GRCh37 / HG19).[16] Ortolog BRCA1 telah diidentifikasi pada sebagian besar vertebrata yang memiliki data genom lengkap.[6]
Fungsi dan mekanisme
BRCA1 adalah bagian dari kompleks protein yang berfungsi memperbaiki kerusakan untai ganda pada DNA. Ketika DNA mengalami kerusakan, untaian pada DNA tersebut akan terputus. Terkadang hanya satu untai yang putus, terkadang kedua untai putus secara bersamaan. Agen pengikat silang DNA (DNAcross-linking agent) adalah salah satu penyebab utama dari kerusakan kromosom dan DNA. Pemutusan untai ganda (double strand breaks) terjadi sebagai intermediet setelah ikatan silang ini dihilangkan. Mutasi bialelik pada BRCA1 telah diidentifikasi bertanggung jawab atas Anemia Fanconi, Complementation Group S (FA-S), penyakit genetik yang terkait dengan hipersensitivitas terhadap agen pengikat silang DNA.[17]
Jenis-jenis perbaikan DNA untai ganda (dsDNA repair)
BRCA1 adalah bagian dari kompleks protein yang memperbaiki DNA ketika kedua untaiannya rusak. Ketika hal ini terjadi, sulit bagi mekanisme perbaikan untuk "mengetahui" cara mengganti urutan DNA yang benar. Ditambah lagi, terdapat berbagai mekanisme perbaikan DNA yang dapat dicoba. Mekanisme perbaikan untai ganda yang melibatkan BRCA1 adalah perbaikan yang diarahkan oleh homologi (homology-directed repair), di mana protein perbaikan menyalin urutan yang identik dari kromatid saudara (sister chromatid) yang masih utuh.[18]
Di dalam nukleus dari berbagai jenis sel normal, protein BRCA1 berinteraksi dengan RAD51 selama perbaikan kerusakan untai ganda DNA.[19] Selain karena radiasi alami atau paparan yang lain, kerusakan ini dapat juga disebabkan ketika kromosom bertukar materi genetik, seperti pada proses rekombinasi homolog (contohnya, crossing over dalam pembelah meiosis). Protein BRCA2, yang memiliki fungsi yang mirip dengan BRCA1, juga berinteraksi dengan protein RAD51. Karena berperan dalam proses perbaikan kerusakan DNA, ketiga protein ini berperan penting dalam menjaga stabilitas genom manusia.[20]
Non homogous end joining (NHEJ)
BRCA1 juga terlibat dalam jenis perbaikan DNA lainnya, yang disebut perbaikan mismatch. BRCA1 berinteraksi dengan protein perbaikan mismatch DNA MSH2.[21] Eksperesi MSH2, MSH6, PARP, dan beberapa protein lain yang terlibat dalam perbaikan untai tunggal diketahui meningkat pada tumor payudara yang memiliki defisiensi BRCA1.[22]
BRCA1 dapat secara langsung berikatan dengan DNA, dengan afinitas yang lebih tinggi untuk struktur DNA yang bercabang (branched structure). Kemampuan untuk mengikat DNA ini berperan pada kemampuan BRCA1 dalam menghambat aktivitas nuklease kompleks MRN, juga aktivitas nuklease Mre11.[23] Hal ini dapat menjelaskan peran BRCA1 untuk memfasilitasi perbaikan DNA dengan ketepatan yang lebih rendah melalui penggabungan ujung non-homolog (non-homologous end joining, NHEJ).[24] BRCA1 juga berkolokalisasi dengan γ-H2AX (histon H2AX terfosforilasi pada serine-139) dalam perbaikan kerusakan untai ganda DNA, yang mengindikasikan bahwa BRCA1 juga berperan dalam merekrut faktor-faktor perbaikan DNA.[25]
Ekspresi BRCA1 yang rendah pada kanker payudara
Kanker payudara berjenis duktal karsinoma in situ
Ekspresi BRCA1 berkurang atau tidak terdeteksi pada sebagian besar kanker payudara duktal tingkat tinggi (high grade ductal breast cancers).[26] Telah lama diketahui bahwa hilangnya aktivitas BRCA1, baik karena mutasi germ-line maupun karena penurunan regulasi ekspresi gen, menyebabkan pembentukan tumor pada jaringan-jaringan tertentu. Secara khusus, penurunan ekspresi BRCA1 berkontribusi pada perkembangan tumor payudara sporadis (tidak diwariskan, terjadi secara spontan) dan yang diwariskan.[27] Ekspresi BRCA1 yang menurun bersifat tumorigenik, karena penurunan ekspresi ini memaikan peran penting dalam perbaikan kerusakan DNA, terutama pemutusan untai ganda, melalui jalur rekombinasi homolog yang berpotensi bebas dari kesalahan.[28] Karena sel yang kekurangan protein BRCA1 cenderung memperbaiki kerusakan DNA dengan mekanisme alternatif yang lebih rentan terhadap kesalahan, penurunan atau penonaktifan protein ini menghasilkan mutasi dan penataan ulang kromosom (chromosomal rearrangemen) yang dapat menyebabkan progresi kanker payudara.[28]
Interaksi Protein
BRCA1 telah terbukti berinteraksi dengan protein-protein berikut:
ABL1[29]
AKT1[30][31]
AR[32]
ATR[33][34][35][36]
ATM[33][34][36][37]
ATF1
BACH1[38]
BARD1[38]
BRCA2[39]
BRCC3
BRE
BRIP1[40][41][42]
C-jun
CHEK2[43][44]
CLSPN[45]
COBRA1[46]
CREBBP[47][48][49][50][51]
CSNK2B[52]
CSTF2[53][54]
CDK2[55][56][57]
DHX9[58][59]
ELK4[60]
EP300[48][50]
ESR1[50][61][62][63]
FANCA[64]
FANCD2[65]
FHL2[66][67]
H2AFX[68]
JUNB[69]
JunD[69]
LMO4[70][71]
MAP3K3[72]
MED1[73]
MED17[74][73][75]
MED21[76]
MED24[73]
MRE11A[77][74][78][79]
MSH2[77]
MSH3[80]
MSH6[77]
Myc[81][82][83]
NBN[77][74][78]
NMI[81]
NPM1
NCOA2[84]
NUFIP1[85]
P53[49][86][87][88]
PALB2[89]
POLR2A[74][76][90][91]
PPP1CA[92]
Rad50[77][74][78]
RAD51[93][94]
RBBP4
Referensi
^ abcGRCm38: Ensembl release 89: ENSMUSG00000017146 - Ensembl, May 2017
^"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.
^ abcYoshida, Kiyotsugu; Miki, Yoshio (2004-11). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer Science (dalam bahasa Inggris). 95 (11): 866–871. doi:10.1111/j.1349-7006.2004.tb02195.x. ISSN 1347-9032.Periksa nilai tanggal di: |date= (bantuan)
^Duncan, J. A.; Reeves, J. R.; Cooke, T. G. (1998-10-01). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular Pathology (dalam bahasa Inggris). 51 (5): 237–247. doi:10.1136/mp.51.5.237. ISSN 1366-8714. PMC395646 . PMID 10193517.Pemeliharaan CS1: Format PMC (link)
^ ab"BRCA1 orthologs". NCBI (dalam bahasa Inggris). Diakses tanggal 2024-03-18.
^Irminger-Finger, Irmgard; Ratajska, Magda; Pilyugin, Maxim (2016-03). "New concepts on BARD1: Regulator of BRCA pathways and beyond". The International Journal of Biochemistry & Cell Biology (dalam bahasa Inggris). 72: 1–17. doi:10.1016/j.biocel.2015.12.008.Periksa nilai tanggal di: |date= (bantuan)
^ abCasaubon, Jesse T.; Kashyap, Sarang; Regan, John-Paul (2024). BRCA1 and BRCA2 Mutations. Treasure Island (FL): StatPearls Publishing. PMID 29262038.
^ abcFriedenson, Bernard (2007-12). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer (dalam bahasa Inggris). 7 (1). doi:10.1186/1471-2407-7-152. ISSN 1471-2407. PMC1959234 . PMID 17683622.Periksa nilai tanggal di: |date= (bantuan)Pemeliharaan CS1: Format PMC (link)
^O'Donovan, P. J.; Livingston, D. M. (2010-06-01). "BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair". Carcinogenesis (dalam bahasa Inggris). 31 (6): 961–967. doi:10.1093/carcin/bgq069. ISSN 0143-3334.
^Wang, Y.; Cortez, D.; Yazdi, P.; Neff, N.; Elledge, S. J.; Qin, J. (2000-04-15). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes & Development. 14 (8): 927–939. ISSN 0890-9369. PMID 10783165.
^Starita, L (2003-06). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology (dalam bahasa Inggris). 15 (3): 345–350. doi:10.1016/S0955-0674(03)00042-5.Periksa nilai tanggal di: |date= (bantuan)
^Hall, Jeff M.; Lee, Ming K.; Newman, Beth; Morrow, Jan E.; Anderson, Lee A.; Huey, Bing; King, Mary-Claire (1990-12-21). "Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21". Science (dalam bahasa Inggris). 250 (4988): 1684–1689. doi:10.1126/science.2270482. ISSN 0036-8075.
^Arney, Kat (2012-02-28). "Tracking down the BRCA1 gene". Cancer Research UK - Cancer News (dalam bahasa Inggris). Diakses tanggal 2024-03-18.
^Miki, Yoshio; Swensen, Jeff; Shattuck-Eidens, Donna; Futreal, P. Andrew; Harshman, Keith; Tavtigian, Sean; Liu, Qingyun; Cochran, Charles; Bennett, L. Michelle (1994-10-07). "A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1". Science (dalam bahasa Inggris). 266 (5182): 66–71. doi:10.1126/science.7545954. ISSN 0036-8075.
^"BRCA1 BRCA1 DNA repair associated [Homo sapiens (human)] - Gene - NCBI". National Center for Biotechnology Information, U.S. National Library of Medicine. Diakses tanggal 2024-03-18.
^Sawyer, Sarah L.; Tian, Lei; Kähkönen, Marketta; Schwartzentruber, Jeremy; Kircher, Martin; University of Washington Centre for Mendelian Genomics; FORGE Canada Consortium; Majewski, Jacek; Dyment, David A. (2015-02-01). "Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype". Cancer Discovery (dalam bahasa Inggris). 5 (2): 135–142. doi:10.1158/2159-8290.CD-14-1156. ISSN 2159-8274. PMC4320660 . PMID 25472942.Pemeliharaan CS1: Format PMC (link)
^Domchek, Susan M.; Tang, Jiangbo; Stopfer, Jill; Lilli, Dana R.; Hamel, Nancy; Tischkowitz, Marc; Monteiro, Alvaro N.A.; Messick, Troy E.; Powers, Jacquelyn (2013-04-01). "Biallelic Deleterious BRCA1 Mutations in a Woman with Early-Onset Ovarian Cancer". Cancer Discovery (dalam bahasa Inggris). 3 (4): 399–405. doi:10.1158/2159-8290.CD-12-0421. ISSN 2159-8274. PMC3625496 . PMID 23269703.Pemeliharaan CS1: Format PMC (link)
^Boulton, S.J. (2006-10-01). "Cellular functions of the BRCA tumour-suppressor proteins". Biochemical Society Transactions (dalam bahasa Inggris). 34 (5): 633–645. doi:10.1042/BST0340633. ISSN 0300-5127.
^Roy, Rohini; Chun, Jarin; Powell, Simon N. (2012-01). "BRCA1 and BRCA2: different roles in a common pathway of genome protection". Nature Reviews Cancer (dalam bahasa Inggris). 12 (1): 68–78. doi:10.1038/nrc3181. ISSN 1474-175X. PMC4972490 . PMID 22193408.Periksa nilai tanggal di: |date= (bantuan)Pemeliharaan CS1: Format PMC (link)
^Wang, Qiang; Zhang, Hongtao; Guerrette, Shawn; Chen, Jinqiu; Mazurek, Anthony; Wilson, Teresa; Slupianek, Artur; Skorski, Tomasz; Fishel, Richard (2001-08-02). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene (dalam bahasa Inggris). 20 (34): 4640–4649. doi:10.1038/sj.onc.1204625. ISSN 0950-9232.
^Warmoes, Marc; Jaspers, Janneke E.; Pham, Thang V.; Piersma, Sander R.; Oudgenoeg, Gideon; Massink, Maarten P.G.; Waisfisz, Quinten; Rottenberg, Sven; Boven, Epie (2012-07). "Proteomics of Mouse BRCA1-deficient Mammary Tumors Identifies DNA Repair Proteins with Potential Diagnostic and Prognostic Value in Human Breast Cancer". Molecular & Cellular Proteomics (dalam bahasa Inggris). 11 (7): M111.013334–1–M111.013334–19. doi:10.1074/mcp.M111.013334. PMC3394939 . PMID 22366898.Periksa nilai tanggal di: |date= (bantuan)Pemeliharaan CS1: Format PMC (link)
^Paull, Tanya T.; Cortez, David; Bowers, Blair; Elledge, Stephen J.; Gellert, Martin (2001-05-22). "Direct DNA binding by Brca1". Proceedings of the National Academy of Sciences (dalam bahasa Inggris). 98 (11): 6086–6091. doi:10.1073/pnas.111125998. ISSN 0027-8424. PMC33426 . PMID 11353843.Pemeliharaan CS1: Format PMC (link)
^Durant, Stephen T.; Nickoloff, Jac A (2005-09-22). "Good Timing in the Cell Cycle for Precise DNA Repair by BRCA1". Cell Cycle (dalam bahasa Inggris). 4 (9): 1216–1222. doi:10.4161/cc.4.9.2027. ISSN 1538-4101.
^Starita, L (2003-06). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology (dalam bahasa Inggris). 15 (3): 345–350. doi:10.1016/S0955-0674(03)00042-5.Periksa nilai tanggal di: |date= (bantuan)
^Wilson, Cindy A.; Ramos, Lillian; Villaseñor, Maria R.; Anders, Karl H.; Press, Michael F.; Clarke, Kathy; Karlan, Beth; Chen, Jun-Jie; Scully, Ralph (1999-02). "Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas". Nature Genetics (dalam bahasa Inggris). 21 (2): 236–240. doi:10.1038/6029. ISSN 1061-4036.Periksa nilai tanggal di: |date= (bantuan)
^Mueller, Christopher R; Roskelley, Calvin D (2002-02). "Regulation of BRCA1 expression and its relationship to sporadic breast cancer". Breast Cancer Research (dalam bahasa Inggris). 5 (1). doi:10.1186/bcr557. ISSN 1465-542X. PMC154136 . PMID 12559046.Periksa nilai tanggal di: |date= (bantuan)Pemeliharaan CS1: Format PMC (link)
^ abJacinto, F. V.; Esteller, M. (2007-07-01). "Mutator pathways unleashed by epigenetic silencing in human cancer". Mutagenesis (dalam bahasa Inggris). 22 (4): 247–253. doi:10.1093/mutage/gem009. ISSN 0267-8357.
^Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M, Favaudon V, Jeggo P (June 2002). "Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation". Mol. Cell. Biol. 22 (12): 4020–32. doi:10.1128/MCB.22.12.4020-4032.2002. PMC133860 . PMID 12024016.
^Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H (November 1999). "Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells". J. Biol. Chem. 274 (45): 32274–8. doi:10.1074/jbc.274.45.32274 . PMID 10542266.
^Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN, Yang Q (December 2008). "Negative Regulation of AKT Activation by BRCA1". Cancer Res. 68 (24): 10040–4. doi:10.1158/0008-5472.CAN-08-3009. PMC2605656 . PMID 19074868.
^Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C (October 2000). "Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (21): 11256–61. Bibcode:2000PNAS...9711256Y. doi:10.1073/pnas.190353897 . PMC17187 . PMID 11016951.
^ abKim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538 . PMID 10608806.
^ abTibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, Abraham RT (December 2000). "Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress". Genes Dev. 14 (23): 2989–3002. doi:10.1101/gad.851000. PMC317107 . PMID 11114888.
^Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage". Cancer Res. 60 (18): 5037–9. PMID 11016625.
^ abGatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies". J. Biol. Chem. 276 (20): 17276–80. doi:10.1074/jbc.M011681200 . PMID 11278964.
^Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B, Khanna KK (June 2000). "Role for ATM in DNA damage-induced phosphorylation of BRCA1". Cancer Res. 60 (12): 3299–304. PMID 10866324.
^ abCantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM (April 2001). "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function". Cell. 105 (1): 149–60. doi:10.1016/S0092-8674(01)00304-X . PMID 11301010.
^Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA (October 2001). "Analysis of murine Brca2 reveals conservation of protein–protein interactions but differences in nuclear localization signals". J. Biol. Chem. 276 (40): 37640–8. doi:10.1074/jbc.M106281200 . PMID 11477095.
^Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G (July 2004). "Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains". Structure. 12 (7): 1137–46. doi:10.1016/j.str.2004.06.002. PMC3652423 . PMID 15242590.
^Yu X, Chini CC, He M, Mer G, Chen J (October 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–42. Bibcode:2003Sci...302..639Y. doi:10.1126/science.1088753. PMID 14576433.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ (June 2004). "Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer". Nature Structural & Molecular Biology. 11 (6): 512–8. doi:10.1038/nsmb775. PMID 15133502.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Lee JS, Collins KM, Brown AL, Lee CH, Chung JH (March 2000). "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response". Nature. 404 (6774): 201–4. Bibcode:2000Natur.404..201L. doi:10.1038/35004614. PMID 10724175.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Chabalier-Taste C, Racca C, Dozier C, Larminat F (December 2008). "BRCA1 is regulated by Chk2 in response to spindle damage". Biochim. Biophys. Acta. 1783 (12): 2223–33. doi:10.1016/j.bbamcr.2008.08.006 . PMID 18804494.
^Lin SY, Li K, Stewart GS, Elledge SJ (April 2004). "Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6484–9. Bibcode:2004PNAS..101.6484L. doi:10.1073/pnas.0401847101 . PMC404071 . PMID 15096610.
^Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (December 2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". J. Cell Biol. 155 (6): 911–21. doi:10.1083/jcb.200108049. PMC2150890 . PMID 11739404.
^Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD (July 2003). "BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit". J. Biol. Chem. 278 (29): 26333–41. doi:10.1074/jbc.M303076200 . PMID 12700228.
^ abPao GM, Janknecht R, Ruffner H, Hunter T, Verma IM (February 2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5. Bibcode:2000PNAS...97.1020P. doi:10.1073/pnas.97.3.1020 . PMC15508 . PMID 10655477.
^ abChai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN (January 1999). "The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter". Oncogene. 18 (1): 263–8. doi:10.1038/sj.onc.1202323 . PMID 9926942.
^ abcFan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (January 2002). "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Res. 62 (1): 141–51. PMID 11782371.
^Neish AS, Anderson SF, Schlegel BP, Wei W, Parvin JD (February 1998). "Factors associated with the mammalian RNA polymerase II holoenzyme". Nucleic Acids Res. 26 (3): 847–53. doi:10.1093/nar/26.3.847. PMC147327 . PMID 9443979.
^O'Brien KA, Lemke SJ, Cocke KS, Rao RN, Beckmann RP (July 1999). "Casein kinase 2 binds to and phosphorylates BRCA1". Biochem. Biophys. Res. Commun. 260 (3): 658–64. doi:10.1006/bbrc.1999.0892. PMID 10403822.
^Kleiman FE, Manley JL (March 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell. 104 (5): 743–53. doi:10.1016/S0092-8674(01)00270-7 . PMID 11257228.
^Wang H, Shao N, Ding QM, Cui J, Reddy ES, Rao VN (Jul 1997). "BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143–57. doi:10.1038/sj.onc.1201252 . PMID 9244350.
^Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH (July 1996). "BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner". Cancer Res. 56 (14): 3168–72. PMID 8764100.
^Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (July 1999). "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): 4843–54. doi:10.1128/MCB.19.7.4843. PMC84283 . PMID 10373534.
^Schlegel BP, Starita LM, Parvin JD (February 2003). "Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells". Oncogene. 22 (7): 983–91. doi:10.1038/sj.onc.1206195 . PMID 12592385.
^Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (July 1998). "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A". Nat. Genet. 19 (3): 254–6. doi:10.1038/930. PMID 9662397.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K, Yezdani M, Reddy ES, Rao VN (March 2001). "c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells". Oncogene. 20 (11): 1357–67. doi:10.1038/sj.onc.1204256 . PMID 11313879.
^Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG (August 2001). "BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9587–92. Bibcode:2001PNAS...98.9587Z. doi:10.1073/pnas.171174298 . PMC55496 . PMID 11493692.
^Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (January 2001). "Role of direct interaction in BRCA1 inhibition of estrogen receptor activity". Oncogene. 20 (1): 77–87. doi:10.1038/sj.onc.1204073 . PMID 11244506.
^Kawai H, Li H, Chun P, Avraham S, Avraham HK (October 2002). "Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells". Oncogene. 21 (50): 7730–9. doi:10.1038/sj.onc.1205971 . PMID 12400015.
^Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, D'Andrea A, Moses R (October 2002). "BRCA1 interacts directly with the Fanconi anemia protein FANCA". Hum. Mol. Genet. 11 (21): 2591–7. doi:10.1093/hmg/11.21.2591 . PMID 12354784.
^Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
^Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q (October 2003). "BRCA1 interacts with FHL2 and enhances FHL2 transactivation function". FEBS Lett. 553 (1–2): 183–9. doi:10.1016/S0014-5793(03)00978-5 . PMID 14550570.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Yan JH, Ye QN, Zhu JH, Zhong HJ, Zheng HY, Huang CF (December 2003). "[Isolation and characterization of a BRCA1-interacting protein]". Yi Chuan Xue Bao (dalam bahasa Tionghoa). 30 (12): 1161–6. PMID 14986435.
^Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage". Curr. Biol. 10 (15): 886–95. doi:10.1016/S0960-9822(00)00610-2 . PMID 10959836.
^ abHu YF, Li R (June 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC186344 . PMID 12080089.
^Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG (October 2003). "Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer. 107 (1): 155–8. doi:10.1002/ijc.11343 . PMID 12925972.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE (March 2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. Biol. Chem. 277 (10): 7849–56. doi:10.1074/jbc.M110603200 . PMID 11751867.
^Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, Andrews HN, McWilliams S, Carty M, Mullan PB, Duprex WP, Liu ET, Johnston PG, Harkin DP (June 2004). "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". Cancer Res. 64 (12): 4148–54. doi:10.1158/0008-5472.CAN-03-4080 . PMID 15205325.
^ abcWada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S (August 2004). "BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220". Oncogene. 23 (35): 6000–5. doi:10.1038/sj.onc.1207786 . PMID 15208681.
^ abcdeChiba N, Parvin JD (October 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200 . PMID 11504724.
^Chiba N, Parvin JD (August 2002). "The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme". Cancer Res. 62 (15): 4222–8. PMID 12154023.
^ abScully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD (May 1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5605–10. Bibcode:1997PNAS...94.5605S. doi:10.1073/pnas.94.11.5605 . PMC20825 . PMID 9159119.
^ abcdeWang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC316544 . PMID 10783165.
^ abcZhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (July 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science. 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999.
^Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. doi:10.1073/pnas.111125998 . PMC33426 . PMID 11353843.
^Rodriguez M, Yu X, Chen J, Songyang Z (December 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200 . PMID 14578343.
^ abLi H, Lee TH, Avraham H (June 2002). "A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer". J. Biol. Chem. 277 (23): 20965–73. doi:10.1074/jbc.M112231200 . PMID 11916966.
^Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM (December 2003). "BRCA1 inhibition of telomerase activity in cultured cells". Mol. Cell. Biol. 23 (23): 8668–90. doi:10.1128/MCB.23.23.8668-8690.2003. PMC262673 . PMID 14612409.
^Zhou C, Liu J (March 2003). "Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells". Biochem. Biophys. Res. Commun. 303 (1): 130–6. doi:10.1016/S0006-291X(03)00318-8. PMID 12646176.
^Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (November 2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509.
^Cabart P, Chew HK, Murphy S (July 2004). "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II". Oncogene. 23 (31): 5316–29. doi:10.1038/sj.onc.1207684 . PMID 15107825.
^Abramovitch S, Werner H (2003). "Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene". Horm. Metab. Res. 35 (11–12): 758–62. doi:10.1055/s-2004-814154. PMID 14710355.Parameter |s2cid= yang tidak diketahui akan diabaikan (bantuan)
^Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H (March 1998). "BRCA1 regulates p53-dependent gene expression". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2302–6. Bibcode:1998PNAS...95.2302O. doi:10.1073/pnas.95.5.2302 . PMC19327 . PMID 9482880.
^Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS (April 1998). "BRCA1 physically associates with p53 and stimulates its transcriptional activity". Oncogene. 16 (13): 1713–21. doi:10.1038/sj.onc.1201932 . PMID 9582019.
^Sy SM, Huen MS, Chen J (April 2009). "PALB2 is an integral component of the BRCA complex required for homologous recombination repair". Proc. Natl. Acad. Sci. U.S.A. 106 (17): 7155–60. Bibcode:2009PNAS..106.7155S. doi:10.1073/pnas.0811159106 . PMC2678481 . PMID 19369211.
^Krum SA, Miranda GA, Lin C, Lane TF (December 2003). "BRCA1 associates with processive RNA polymerase II". J. Biol. Chem. 278 (52): 52012–20. doi:10.1074/jbc.M308418200 . PMID 14506230.
^Krum SA, Womack JE, Lane TF (September 2003). "Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity". Oncogene. 22 (38): 6032–44. doi:10.1038/sj.onc.1206515 . PMID 12955082.
^Liu Y, Virshup DM, White RL, Hsu LC (November 2002). "Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha". Cancer Res. 62 (22): 6357–61. PMID 12438214.
^Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R (September 1998). "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells". Mol. Cell. 2 (3): 317–28. doi:10.1016/S1097-2765(00)80276-2 . PMID 9774970.
^Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (January 1997). "Association of BRCA1 with Rad51 in mitotic and meiotic cells". Cell. 88 (2): 265–75. doi:10.1016/S0092-8674(00)81847-4 . PMID 9008167.