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-Structure paper
タイトル | Structural analysis of BRCA1 reveals modification hotspot. |
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ジャーナル・号・ページ | Sci Adv, Vol. 3, Issue 9, Page e1701386, Year 2017 |
掲載日 | 2017年9月20日 |
![]() | Yanping Liang / William J Dearnaley / A Cameron Varano / Carly E Winton / Brian L Gilmore / Nick A Alden / Zhi Sheng / Deborah F Kelly / ![]() |
PubMed 要旨 | Cancer cells afflicted with mutations in the breast cancer susceptibility protein (BRCA1) often suffer from increased DNA damage and genomic instability. The precise manner in which physical changes ...Cancer cells afflicted with mutations in the breast cancer susceptibility protein (BRCA1) often suffer from increased DNA damage and genomic instability. The precise manner in which physical changes to BRCA1 influence its role in DNA maintenance remains unclear. We used single-particle electron microscopy to study the three-dimensional properties of BRCA1 naturally produced in breast cancer cells. Structural studies revealed new information for full-length BRCA1, engaging its nuclear binding partner, the BRCA1-associated RING domain protein (BARD1). Equally important, we identified a region in mutated BRCA1 that was highly susceptible to ubiquitination. We refer to this site as a modification "hotspot." Ubiquitin adducts in the hotspot region proved to be biochemically reversible. Collectively, we show how key changes to BRCA1 affect its structure-function relationship, and present new insights to potentially modulate mutated BRCA1 in human cancer cells. |
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手法 | EM (単粒子) |
解像度 | 14.5 - 14.7 Å |
構造データ | ![]() EMDB-8833: ![]() EMDB-8834: |
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