BRCA1

3. 유전자

1990년 캘리포니아대학교 버클리캠퍼스(UC Berkeley)의 메리-클레어 킹 연구팀이 BRCA1의 염색체 위치를 발견했다.^[14] 1994년 유타 대학교, 국립환경보건과학연구소(NIEHS), 마이리어드 제네틱스(Myriad Genetics)의 과학자들이 이 유전자를 클로닝했다.^[115][16]

대부분의 척추동물에서 ''BRCA1''의 상동유전자가 확인되었다.^[2] BRCA1 유전자는 17번 염색체 장완(q arm)의 중심절(セントロメア)에 가까운 17q21.32 영역에 위치한다.^[223]

4. 단백질 구조

BRCA1 단백질은 다음과 같은 도메인을 포함한다.^[17]

• 아연 손가락, C3HC4 유형 (RING finger)
• BRCA1 C 말단 (BRCT) 도메인

4. 1. 아연 RING finger domain

4. 2. 세린 클러스터 도메인

4. 3. BRCT 도메인

5. 기능 및 메커니즘

BRCA1은 DNA의 이중 가닥 절단을 복구하는 복합체의 일부이다. DNA 이중 나선의 가닥은 손상될 때 지속적으로 끊어지는데, 때로는 한 가닥만 끊어지기도 하고, 때로는 두 가닥 모두 동시에 끊어지기도 한다. BRCA1은 두 가닥 모두 끊어졌을 때 DNA를 복구하는 단백질 복합체의 일부이며, 상동 재조합 메커니즘에 관여한다. 이 메커니즘에서 복구 단백질은 손상되지 않은 자매 염색분체에서 동일한 서열을 복사한다.^[28]

정상 세포의 핵에서 BRCA1 단백질은 DNA 이중 가닥 절단 복구 과정에서 RAD51과 상호작용한다.^[30] 염색체가 유전 물질을 교환할 때(상동 재조합, 예: 감수 분열 중 "교차")에도 이러한 절단이 발생할 수 있다. BRCA1과 유사한 기능을 하는 BRCA2 단백질도 RAD51 단백질과 상호작용하며, 이 세 단백질은 DNA 손상 복구에 영향을 미쳐 인간 게놈의 안정성을 유지하는 역할을 한다.^[31]

BRCA1은 불일치 복구에도 관여하며, DNA 불일치 복구 단백질인 MSH2와 상호작용한다.^[32] 발로신 함유 단백질(VCP, p97)은 손상된 DNA 부위에 BRCA1을 모집하는 역할을 하며, BRCA1은 VCP와 상호작용한다.^[218] BRCA1은 c-Myc 및 게놈 안정성 유지에 중요한 다른 단백질과도 상호작용한다.^[35]

BRCA1은 분지형 DNA 구조에 대해 더 높은 친화력을 가지며 DNA에 직접 결합한다. 이 능력은 MRN 복합체와 Mre11 자체의 뉴클레아제 활성을 억제하는 데 기여하며,^[36] 이는 BRCA1이 비상동 말단 결합(NHEJ)에 의한 낮은 충실도 DNA 복구를 촉진하는 역할을 설명할 수 있다.^[37] BRCA1은 또한 DNA 이중 가닥 절단 복구 초점에서 γ-H2AX (세린-139에서 인산화된 히스톤 H2AX)와 공동으로 국재화되어 복구 인자를 모집하는 데 역할을 할 수 있음을 나타낸다.^[11][145]

BRCA1은 DNA 손상 시 신호 전달에 중요한 역할을 하며, 세포 주기에 따라 인산화를 받을 뿐만 아니라 DNA 손상에 따라 인산화를 받는다. 인산화된 BRCA1은 RAD51 등의 DNA 복구 단백질과 협력하여 DNA 손상을 복구한다.^[226]

6. 전사

BRCA1은 RNA 중합효소 II 홀로효소의 구성 요소로 추정되었으나, 후속 연구에서 SWI/SNF 크로마틴 개조 복합체와 상호작용하는 것으로 밝혀졌다. 또한 음성 신장 인자 (NELF) 복합체의 COBRA1 서브유닛과 상호작용한다.

7. 돌연변이와 암 위험

BRCA1 유전자의 발현 감소는 고등급 관상피 유방암에서 흔하게 나타나며, 이는 생식세포 돌연변이나 유전자 발현 하향 조절을 통해 종양 형성을 유발한다.^[51][52] BRCA1은 이중 가닥 절단과 같은 DNA 손상을 복구하는 상동 재조합 경로에 중요한 역할을 한다.^[53] BRCA1 단백질이 부족하면 오류 발생 가능성이 높은 메커니즘으로 DNA 손상을 복구하게 되어 돌연변이와 염색체 재배열을 일으켜 유방암으로 진행될 수 있다.^[53]

BRCA1 발현은 상피성 난소암(EOCs)의 55%에서 낮게 나타나며, 특히 장액성 난소암의 경우 50% 이상에서 BRCA1 발현이 낮다.^[54][55] BRCA1 결핍으로 인한 상동 재조합 복구 결함은 고등급 장액성 난소암의 진행과 치료 반응에 영향을 미치는 분자 사건을 유발한다.^[56]

BRCA1은 이온화 방사선 등 DNA 손상 유발 물질에 의해 세포에 스트레스가 가해질 때 세포자멸사를 촉진한다.^[57] DNA 손상 복구와 세포자멸사는 게놈 무결성 유지에 필수적이다. DNA 복구 결핍 세포는 DNA 손상이 축적되고, 세포자멸사에 결함이 있으면 과도한 DNA 손상에도 생존하여 돌연변이를 통한 암 발생 가능성이 커진다.^[58]

1990년 캘리포니아 대학교 버클리캠퍼스의 메리-클레어 킹 연구팀은 조기 발병 가족성 유방암의 원인 유전자가 17번 염색체 장완에 존재함을 발견했고,^[224] 1994년 유타 대학교의 미키 요시오 연구팀이 BRCA1을 확인했다.^[225]

BRCA1은 DNA 손상 시 신호 전달에 중요하며, 세포 주기 및 DNA 손상에 따라 인산화된다. 인산화된 BRCA1은 RAD51 등 DNA 복구 단백질과 협력하여 DNA 손상을 복구한다.^[226] RAD51은 DNA 나선 구조를 풀고 상동성을 이용해 손상된 DNA 복구를 돕지만, BRCA1이나 BRCA2에 변이가 있으면 DNA 복구가 제대로 이루어지지 않는다. 배양 세포 실험에서 BRCA1 기능이 부분적으로 상실된 세포는 X선에 대한 감수성이 높았다.^[227] BRCA1 변이를 동반하는 가족성 유방암 가계에서는 젊은 나이의 유방암, 양측성 유방암, 난소암 동반 발병 빈도가 높다. BRCA1과 BRCA2 변이를 모두 가지면 유방암 평생 발병률이 80% 이상이다(미국 데이터).^[228]

8. BRCA1 발현 저하와 암

고등급 관상피 유방암 및 상피성 난소암에서 BRCA1 발현이 감소하거나 검출되지 않는 경우가 많다. 유방암 종양에서 자주 발견되는 특정 잠복 바이러스는 BRCA1 유전자의 발현을 감소시켜 유방 종양 발생을 유발할 수 있다.^[61] BRCA1 발현 감소는 DNA 손상 복구 능력 저하로 이어져 돌연변이 및 염색체 재배열을 유발하고, 암 발생 위험을 높인다.

8. 1. BRCA1 돌연변이와 암

8. 2. BRCA1 프로모터 과메틸화와 암

8. 3. 마이크로RNA에 의한 BRCA1 발현 억제

9. 생식세포 계열 돌연변이와 창시자 효과

특정 집단에서 흔하게 나타나는 ''BRCA1'' 종자 돌연변이는 공통 조상으로부터 유래했을 가능성을 시사한다. 아슈케나지 유대인, 네덜란드인, 폴란드인 등 여러 인구 집단에서 창시자 돌연변이가 발견되었다. 한국인 ''BRCA1/2'' 유전자 변이 양성자 719명을 대상으로 진행한 연구 결과, 한국인에게 특이적인 18개의 ''BRCA1/2'' 유전자 반복 변이가 관찰되었다. 이는 ''BRCA1/2'' 유전자 검사의 해석에 중요한 정보를 제공한다.^[68] DNA 복구가 결핍되면 DNA 손상이 축적되는 경향이 있다. 이러한 과도한 DNA 손상은 오류 발생이 잦은 손상 회피 합성으로 인해 DNA 복제 과정에서 돌연변이 오류를 증가시킬 수 있다. 또한 과도한 DNA 손상은 DNA 복구 과정에서 발생하는 오류로 인해 후성유전학적 변화를 증가시킬 수 있다.^[69][70]

10. 여성 생식능

BRCA1은 DNA 손상 시 신호 전달에 중요한 역할을 하며, 세포 주기에 따라 인산화를 받는 것으로 알려져 있다. 인산화된 BRCA1은 RAD51 등의 DNA 복구 단백질과 협력하여 DNA 손상을 복구한다. BRCA1에 변이가 있으면 DNA 복구가 제대로 되지 않아 난소 노화, 생식력 저하, 조기 폐경 등을 유발할 수 있다.^[226][227]

11. 암 화학요법

비소세포폐암(NSCLC) 환자는 종종 DNA에 가교 결합을 유발하는 백금 화합물(예: 시스플라틴, 카보플라틴, 옥살리플라틴)로 치료받는다. 1차 종양에서 BRCA1 발현이 낮은 비소세포폐암 환자는 백금 기반 화학요법 후 생존율이 향상되는 경향을 보인다.^[112][113] 이는 암에서 BRCA1이 낮고 DNA 복구 수준이 낮으면 DNA 가교 결합제에 의한 치료에 더 취약해지기 때문이다. 높은 BRCA1은 백금 약물에 의해 유도된 DNA 손상을 제거하여 암세포를 보호할 수 있다. 따라서 BRCA1 발현 수준은 폐암 화학요법을 맞춤화하는 데 중요한 도구가 될 수 있다.^[112][113]

BRCA1 발현 수준은 난소암 치료와도 관련이 있다. 백금 약물로 치료받은 산발성 난소암 환자 중, BRCA1 발현이 낮은 환자(46개월)는 BRCA1 발현이 높은 환자(33개월)보다 중앙 생존 기간이 더 길었다.^[114]

12. 특허, 시행, 소송 및 논란

마이리어드 제네틱스는 BRCA1 유전자 및 관련 진단 방법에 대한 특허를 출원하여 독점적 라이선스를 보유하고, 이를 미국 내 임상 진단 연구소에 대해 집행해 왔다.^[115][13] 이러한 사업 모델은 마이리어드가 성장하는 데 기여했지만,^[12] 높은 검사 비용과 다른 연구소의 2차 소견을 받을 수 없다는 점 때문에 논란이 있었다.^[13][117] 이는 ''유전자검사협회 대 마이리어드 제네틱스 소송''으로 이어졌다.^[13][117]

2013년 6월, 미국 연방 대법원은 "자연적으로 발생하는 DNA 구간은 자연의 산물이며 단순히 분리되었다는 이유만으로 특허 자격이 있는 것은 아니다"라고 판결하여 BRCA1 및 BRCA2 유전자에 대한 마이리어드의 특허를 무효화했다.^[122] 그러나 법원은 자연계에 없는 것을 만들기 위해 유전자를 조작한 경우에는 여전히 특허 보호를 받을 수 있다고 판결했다.^[122]

호주 연방 법원은 2013년 2월 BRCA1 유전자에 대한 호주 마이리어드 제네틱스 특허의 유효성을 인정했지만,^[123] 2015년 10월 7일 호주 고등법원은 "고등법원은 유방암과 난소암의 발병 가능성을 나타내는 표준과 특정한 변이가 있는 BRCA1 단백질을 코딩하는 분리된 핵산이 '특허 가능한 발명'이 아니라고 판결했습니다."라며 마이리어드 제네틱스에 대한 소송에서 원고의 손을 들어주었다.^[125]

마이리어드 제네틱스(Myriad Genetics)사는 BRCA1 및 BRCA2 유전자 분리 및 동정에 관한 기술에 대해 미국에서 특허를 취득했으나,^[231] 미국 자유권 협회(American Civil Liberties Union)가 제기한 소송에서 2010년 5월 29일 뉴욕 지방법원에서 특허 무효 판결이 내려졌다.^[232][233] 이후 항소와 상고를 거쳐,^[234] 2013년 6월 미국 연방대법원에서 최종적으로 특허 무효 판결이 선고되었다.^[237] 대법원은 "자연의 DNA 서열은 자연의 산물이며, 지금까지 발견되지 않았던 것을 단순히 분리했다는 것만으로는 특허가 될 수 없다."는 이유를 들었다.^[237]

13. 상호작용

BRCA1은 다음과 같은 단백질들과 상호작용하는 것으로 알려져 있다.

참조

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_[33] 논문 Proteomics of mouse BRCA1-deficient mammary tumors identifies DNA repair proteins with potential diagnostic and prognostic value in human breast cancer 2012-07-01
_[34] 논문 The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks 2011-11-01
_[35] 논문 BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells 1998-10-01
_[36] 논문 Direct DNA binding by Brca1
_[37] 논문 Good timing in the cell cycle for precise DNA repair by BRCA1
_[38] 논문 Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde 2007-12-01
_[39] 논문 Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins 2015-04-01
_[40] 서적 GeneReviews University of Washington, Seattle 2016-12-01
_[41] 웹사이트 Genetics http://www.breastcan[...] Breastcancer.org 2012-09-17
_[42] 논문 BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants 2006-01-01
_[43] 논문 Genomic rearrangements in the BRCA1 and BRCA2 genes 2005-05-01
_[44] 논문 Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families 2004-02-01
_[45] 논문 Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method 2003-04-01
_[46] 논문 Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments 2002-09-01
_[47] 논문 High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1 2007-09-01
_[48] 논문 Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors
_[49] 논문 Novel genetic variants in microRNA genes and familial breast cancer 2009-03-01
_[50] 논문 Evidence that BRCA1- or BRCA2-associated cancers are not inevitable
_[51] 논문 Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas
_[52] 논문 Regulation of BRCA1 expression and its relationship to sporadic breast cancer
_[53] 논문 Mutator pathways unleashed by epigenetic silencing in human cancer
_[54] 논문 miR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition
_[55] 논문 Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma
_[56] 논문 The genesis and evolution of high-grade serous ovarian cancer
_[57] 논문 BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell lines 2000-10-27
_[58] 논문 DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis 2002-06-01
_[59] 논문 Breast cancer susceptibility genes. BRCA1 and BRCA2
_[60] 논문 Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas
_[61] 논문 How latent viruses cause breast cancer: An explanation based on the microcompetition model 2019-08-01
_[62] 논문 Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors
_[63] 논문 miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors
_[64] 논문 MicroRNA-182-5p targets a network of genes involved in DNA repair
_[65] 논문 Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers
_[66] 논문 MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma
_[67] 논문 DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture
_[68] 논문 The DNA damage response: ten years after
_[69] 논문 Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island
_[70] 논문 DNA damage, homology-directed repair, and DNA methylation 2007-07-01
_[71] 논문 The "portrait" of hereditary breast cancer
_[72] 논문 The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals 1995-10-01
_[73] 논문 BRCA1 mutations in Ashkenazi Jewish women
_[74] 논문 BRCA1 and BRCA2: 1994 and beyond
_[75] 논문 Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion
_[76] 논문 Founder populations and their uses for breast cancer genetics
_[77] 논문 BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families 2004-07-01
_[78] 논문 BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer 2015-11-01
_[79] 논문 BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics
_[80] 논문 A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families
_[81] 논문 Mutation analysis of the BRCA1 and BRCA2 genes in the Belgian patient population and identification of a Belgian founder mutation BRCA1 IVS5 + 3A > G
_[82] 논문 BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients https://repub.eur.nl[...]
_[83] 논문 Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families
_[84] 논문 Evidence of founder mutations in Finnish BRCA1 and BRCA2 families
_[85] 논문 Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population
_[86] 논문 BRCA1 testing in breast and/or ovarian cancer families from northeastern France identifies two common mutations with a founder effect
_[87] 논문 Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history
_[88] 논문 Frequency of BRCA1 mutation 5382insC in German breast cancer patients
_[89] 웹사이트 Mutation data of the BRCA1 gene http://mutview.dmb.m[...] Keio University
_[90] 논문 Germ line BRCA1 and BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed
_[91] 논문 Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary
_[92] 논문 Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer
_[93] 논문 Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population
_[94] 논문 A BRCA1 mutation in Native North American families
_[95] 논문 BRCA1 and BRCA2 mutations in Scotland and Northern Ireland
_[96] 논문 BRCA1 1675delA and 1135insA account for one third of Norwegian familial breast-ovarian cancer and are associated with later disease onset than less frequent mutations
_[97] 논문 The Norwegian founder mutations in BRCA1: high penetrance confirmed in an incident cancer series and differences observed in the risk of ovarian cancer
_[98] 논문 Contribution of BRCA1 and BRCA2 Mutations to Breast and Ovarian Cancer in Pakistan
_[99] 논문 Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer
_[100] 논문 BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland 2003-05-01
_[101] 논문 Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia 1997-05-01
_[102] 논문 Evidence of a founder BRCA1 mutation in Scotland 2000-02-01
_[103] 논문 The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript 2001-06-01
_[104] 논문 Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain 2003-04-01
_[105] 논문 The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation 2001-10-01
_[106] 논문 A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause 2008-03-01
_[107] 논문 Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew 2009-12-01
_[108] 논문 Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks 2010-01-01
_[109] 논문 Premature menopause in patients with BRCA1 gene mutation 2006-11-01
_[110] 논문 Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans 2013-02-01
_[111] 서적 Advances in Genetics 1987
_[112] 논문 BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer 2004-10-01
_[113] 논문 ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer 2012-04-01
_[114] 논문 The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer 2009-02-01
_[115] 특허 7Q-linked breast and ovarian cancer susceptibility gene
_[116] 특허 Chromosome 13-linked breast cancer susceptibility gene
_[117] 뉴스 ACLU sues over patents on breast cancer genes http://edition.cnn.c[...] CNN 2009-05-14
_[118] 논문 Impact of gene patents and licensing practices on access to genetic testing for inherited susceptibility to cancer: comparing breast and ovarian cancers with colon cancers 2010-04-01
_[119] 논문 European groups oppose Myriad's latest patent on BRCA1 2003-01-01
_[120] 웹사이트 How Will Myriad Respond to the Next Generation of BRCA Testing? http://www.genomicsl[...] Robinson, Bradshaw, and Hinson 2011-03-01
_[121] 웹사이트 Genetics and Patenting http://www.ornl.gov/[...] U.S. Department of Energy Genome Programs 2010-07-07
_[122] 뉴스 Supreme Court Rules Human Genes May Not Be Patented https://www.nytimes.[...] 2013-06-13
_[123] 뉴스 Landmark patent ruling over breast cancer gene BRCA1 http://www.smh.com.a[...] 2013-02-15
_[124] 뉴스 Australian federal court rules isolated genetic material can be patented https://www.theguard[...] 2014-09-05
_[125] 뉴스 Patient wins high court challenge against company's cancer gene patent https://www.theguard[...] 2015-10-07
_[126] 논문 Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation 2002-06-01
_[127] 논문 Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells 1999-11-01
_[128] 논문 Negative Regulation of AKT Activation by BRCA1 2008-12-01
_[129] 논문 Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells 2000-10-01
_[130] 논문 Substrate specificities and identification of putative substrates of ATM kinase family members 1999-12-01
_[131] 논문 Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress 2000-12-01
_[132] 논문 Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage 2000-09-01
_[133] 논문 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 2001-05-01
_[134] 논문 Role for ATM in DNA damage-induced phosphorylation of BRCA1 2000-06-01
_[135] 논문 Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks 1999-11-01
_[136] 논문 BRCA1 physically and functionally interacts with ATF1 2000-11-01
_[137] 논문 BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function 2001-04-01
_[138] 논문 Analysis of murine Brca2 reveals conservation of protein–protein interactions but differences in nuclear localization signals 2001-10-01
_[139] 논문 Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains 2004-07-01
_[140] 논문 The BRCT domain is a phospho-protein binding domain 2003-10-01
_[141] 논문 Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer 2004-06-01
_[142] 논문 hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response 2000-03-01
_[143] 논문 BRCA1 is regulated by Chk2 in response to spindle damage 2008-12-01
_[144] 논문 Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation 2004-04-01
_[145] 논문 BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations 2001-12-01
_[146] 논문 BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit 2003-07-01
_[147] 논문 CBP/p300 interact with and function as transcriptional coactivators of BRCA1 2000-02-01
_[148] 논문 The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter 1999-01-01
_[149] 논문 p300 Modulates the BRCA1 inhibition of estrogen receptor activity 2002-01-01
_[150] 논문 Factors associated with the mammalian RNA polymerase II holoenzyme 1998-02-01
_[151] 논문 Casein kinase 2 binds to and phosphorylates BRCA1 1999-07-01
_[152] 논문 The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression 2001-03-01
_[153] 논문 Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50 1999-09-01
_[154] 논문 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 1997-07-01
_[155] 논문 BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner 1996-07-01
_[156] 논문 BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site 1999-07-01
_[157] 논문 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 2003-02-01
_[158] 논문 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A 1998-07-01
_[159] 논문 c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells 2001-03-01
_[160] 논문 BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor 2001-08-01
_[161] 논문 Role of direct interaction in BRCA1 inhibition of estrogen receptor activity 2001-01-01
_[162] 논문 Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells 2002-10-01
_[163] 논문 BRCA1 interacts directly with the Fanconi anemia protein FANCA 2002-10-01
_[164] 논문 Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport 2003-10-01
_[165] 논문 BRCA1 interacts with FHL2 and enhances FHL2 transactivation function 2003-10-01
_[166] 논문 [Isolation and characterization of a BRCA1-interacting protein] 2003-12-01
_[167] 논문 A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
_[168] 논문 JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction 2002-06-01
_[169] 논문 Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas 2003-10-01
_[170] 논문 The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity 2002-03-01
_[171] 논문 BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3 2004-06-01
_[172] 논문 Redistribution of BRCA1 among four different protein complexes following replication blockage 2001-10-01
_[173] 논문 The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme 2002-08-01
_[174] 논문 BRCA1 is a component of the RNA polymerase II holoenzyme 1997-05-01
_[175] 논문 BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures 2000-04-01
_[176] 논문 Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains 2003-12-00
_[177] 논문 BRCA1 inhibition of telomerase activity in cultured cells 2003-12-00
_[178] 논문 Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells 2003-03-00
_[179] 논문 A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer 2002-06-00
_[180] 논문 Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor 2000-11-00
_[181] 논문 BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II 2004-07-00
_[182] 논문 Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene
_[183] 논문 BRCA1 regulates p53-dependent gene expression 1998-03-00
_[184] 논문 BRCA1 physically associates with p53 and stimulates its transcriptional activity 1998-04-00
_[185] 논문 PALB2 is an integral component of the BRCA complex required for homologous recombination repair 2009-04-00
_[186] 논문 BRCA1 associates with processive RNA polymerase II 2003-12-00
_[187] 논문 Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity 2003-09-00
_[188] 논문 Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha 2002-11-00
_[189] 논문 Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response 1999-07-00
_[190] 논문 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells 1998-09-00
_[191] 논문 Association of BRCA1 with Rad51 in mitotic and meiotic cells 1997-01-00
_[192] 논문 BRCA1 interacts with components of the histone deacetylase complex 1999-04-00
_[193] 논문 Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCA1 2001-06-00
_[194] 논문 Identification of proteins that interact with BRCA1 by Far-Western library screening https://zenodo.org/r[...]
_[195] 논문 The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression 1998-09-00
_[196] 논문 Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage 1999-04-00
_[197] 논문 Characterization of a carboxy-terminal BRCA1 interacting protein 1998-11-00
_[198] 논문 Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response 2000-07-00
_[199] 논문 Effect of DNA damage on a BRCA1 complex 2001-11-00
_[200] 논문 Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor 2000-06-00
_[201] 논문 BRCA1-associated growth arrest is RB-dependent 1999-10-00
_[202] 논문 Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding 2001-08-00
_[203] 논문 BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or Mdm2 2004-04-00
_[204] 논문 BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer 2000-07-00
_[205] 논문 Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes 2000-05-00
_[206] 서적 Genome Stability and Human Diseases Springer 2012-04-00
_[207] 논문 Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains 2002-12-00
_[208] 논문 Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex 2003-05-00
_[209] 논문 Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase 2004-02-00
_[210] 논문 Control of biochemical reactions through supramolecular RING domain self-assembly 2002-11-00
_[211] 저널 Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase 2002-06-00
_[212] 저널 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair 2003-11-00
_[213] 저널 Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase 2004-07-00
_[214] 저널 BRCA1-independent ubiquitination of FANCD2 2003-07-00
_[215] 저널 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin 2003-09-00
_[216] 저널 The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation 2001-05-00
_[217] 저널 Novel consensus DNA-binding sequence for BRCA1 protein complexes https://zenodo.org/r[...] 2003-10-00
_[218] 저널 VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells 2000-05-00
_[219] 저널 Association of BRCA1 with the inactive X chromosome and XIST RNA 2004-01-00
_[220] 저널 BRCA1 supports XIST RNA concentration on the inactive X chromosome 2002-11-00
_[221] 저널 Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1 2000-10-00
_[222] 웹사이트 유방암、난소암의 억제 유전자의 작용을 돕는 단백질 SCAI를 신발견 https://resou.osaka-[...] 오사카대학 2017-07-12
_[223] 웹사이트 BRCA1 breast cancer 1, early onset -Homo sapiens (human) - http://www.ncbi.nlm.[...] National Center for Biotechnology Information, U.S. National Library of Medicine 2015-06-15
_[224] 간행물 BRCA１と DNA 損傷応答 http://www.jbsoc.or.[...] 生化学 2012-00-00
_[225] 논문 A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 1994-00-00
_[226] 서적 가족성 유방암 원인 유전자 토이 마사카즈 편 「유방암의 기초와 임상」
_[227] 서적 와인버그 암 생물학 남강당
_[228] 뉴스 안젤리나 졸리, 양측 유방 절제 수술…유전성 암 예방 https://www.cnn.co.j[...] CNN
_[229] 논문 Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers http://www.nejm.org/[...] 2009-07-09
_[230] 저널 Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation 2018-00-00
_[231] 특허 7Q-linked breast and ovarian cancer susceptibility gene 1998-05-05
_[232] 뉴스 ACLU sues over patents on breast cancer genes http://edition.cnn.c[...] CNN 2009-05-14
_[233] 웹사이트 Legal Decision http://www.aclu.org/[...] United States District Court Southern District of New York 2010-03-29
_[234] 웹사이트 BRCA1/2 patents ruled invalid in PUBPAT/ACLU lawsuit http://nysbar.com/bl[...] (S U P R A S P I N A T U S) 2010-03-30
_[235] 웹사이트 US Court upholds Myriad's breast cancer gene patents http://blogs.nature.[...] Nature News Blog
_[236] 웹사이트 blogs.nature.com http://blogs.nature.[...] blogs.nature.com
_[237] 웹사이트 Association for Molecular Pathology v. Myriad Genetics o. 12-398 http://www.scotusblo[...] SCOTUS blog
_[238] 저널 BRCA1 and BRCA2 proteins: roles in health and disease 1998-10-00
_[239] 저널 Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage https://archive.org/[...] 2004-11-00
_[240] 웹인용 BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There http://www.healthcen[...] HealthCentral 2007-05-29
_[241] 웹인용 BRCA: What we know now http://www.cap.org/a[...] College of American Pathologists 2006-09-01
_[242] 저널 The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers 2007-08-00
_[243] 웹인용 Breast cancer genes protect against some leukemias and lymphomas http://www.scivee.tv[...] SciVee 2008-06-08
_[244] 웹인용 BRCA Decision Tool http://brcatool.stan[...] 2017-02-19
_[245] 웹인용 [유명인과 질병] 안젤리나 졸리의 「예방적 유방절제술」선택 존중해야 http://hosp.ajoumc.o[...] 2021-04-23
_[246] 저널 Linkage of early-onset familial breast cancer to chromosome 17q21 1990-12-01
_[247] 웹사이트 High-Impact Science: Tracking down the BRCA genes (Part 1) http://scienceblog.c[...] 2012-02-28
_[248] 특허 7Q-linked breast and ovarian cancer susceptibility gene 1998-05-05
_[249] 저널 A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 1994-10-01