生物谷報(bào)道：研究人員報(bào)告說，一組復(fù)合蛋白質(zhì)與腫瘤抑制基因（也被稱為乳腺癌易患基因）BRCA1一起工作來修復(fù)DNA,。雖然BRCA1的確切功能現(xiàn)在仍然不清楚,，但是這些發(fā)現(xiàn)給對癌癥發(fā)展和治療感興趣的研究人員提供了該基因的更多線索,，BRCA1的突變與乳腺癌、卵巢癌,、輸卵管癌,、前列腺癌、以及結(jié)腸癌有關(guān),。
Bin Wang和共同作者發(fā)表在最新一期《科學(xué)》雜志上的研究顯示,，BRCA1被合作伙伴蛋白質(zhì)Abraxas和Rap80調(diào)動到DNA修復(fù)位置來修復(fù)DNA受損的細(xì)胞,。Abraxas蛋白質(zhì)調(diào)解Rap80和BRCA1的相互作用。Rap80被招到有DNA損傷的細(xì)胞的一個(gè)部位,。根據(jù)Bijan Sobhian和同事,、以及Hongtae Kim和共同作者的報(bào)告，Raps80將BRCA1標(biāo)定到DNA損傷的位置,，并且在正確的DNA損傷修復(fù)響應(yīng)中起關(guān)鍵作用,。在一項(xiàng)涉及DNA損傷修復(fù)系統(tǒng)的調(diào)節(jié)響應(yīng)有關(guān)蛋白質(zhì)的大規(guī)模研究中，Shuhei Matsuoka和同事發(fā)現(xiàn)了900多個(gè)涉及700多個(gè)蛋白質(zhì)的位置,。這個(gè)新數(shù)據(jù)庫揭示了比期待的更大的DNA損傷響應(yīng)網(wǎng)絡(luò),，同時(shí)顯示帶有DNA損傷的細(xì)胞完全改變了其生理特征。這個(gè)數(shù)據(jù)庫是研究癌癥和神經(jīng)退化疾病的研究人員尋找新候選基因的資源,。John H. J. Petrini針對四篇相關(guān)的論文撰寫了一篇研究評述,。
原始出處:
Science 25 May 2007:
Vol. 316. no. 5828, pp. 1194 - 1198
DOI: 10.1126/science.1139476
Reports
Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response
Bin Wang,1 Shuhei Matsuoka,1 Bryan A. Ballif,2* Dong Zhang,1 Agata Smogorzewska,1,3 Steven P. Gygi,2 Stephen J. Elledge1
The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through a phospho-Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1 (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein), forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting motif (UIM)–containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were required for DNA damage resistance, G2-M checkpoint control, and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation, and the UIM domains alone were capable of foci formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites in part through recognition of ubiquitinated proteins.
1 Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
3 Department of Pathology, Massachusetts General Hospital, Boston, MA 02214, USA.
* Present address: Department of Biology, University of Vermont, Burlington, VT 05405, USA.
Present address: Genomic Instability Group, Oncology Research, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA.
To whom correspondence should be addressed. E-mail: [email protected]
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