+検索条件
-Structure paper
タイトル | Correcting errors in the BRCA1 warning system. |
---|---|
ジャーナル・号・ページ | DNA Repair (Amst), Vol. 73, Page 120-128, Year 2019 |
掲載日 | 2018年11月22日 |
著者 | Yanping Liang / William J Dearnaley / Nick A Alden / Maria J Solares / Brian L Gilmore / Kevin J Pridham / A Cameron Varano / Zhi Sheng / Elizabeth Alli / Deborah F Kelly / |
PubMed 要旨 | Given its important role in human health and disease, remarkably little is known about the full-length three-dimensional (3D) molecular architecture of the breast cancer type 1 susceptibility protein ...Given its important role in human health and disease, remarkably little is known about the full-length three-dimensional (3D) molecular architecture of the breast cancer type 1 susceptibility protein (BRCA1), or its mechanisms to engage the tumor suppressor, TP53 (p53). Here, we show how a prevalent cancer-related mutation in the C-terminal region of the full-length protein, BRCA1, affects its structural properties, yet can be biochemically corrected to restore its functional capacity. As a downstream consequence of restoring the ubiquitin ligase activity of mutated BRCA1, the DNA repair response of p53 was enhanced in cellular extracts naturally deficient in BRCA1 protein expression. Complementary structural insights of p53 tetramers bound to DNA in different stage of the repair process support these biochemical findings in the context of human cancer cells. Equally important, we show how this knowledge can be used to lower the viability of breast cancer cells by modulating the stability of the BRCA1 protein and its associated players. |
リンク | DNA Repair (Amst) / PubMed:30503669 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 15.5 - 20.1 Å |
構造データ | EMDB-8926: EMDB-8927: |
由来 |
|