一个含有结构性DNA结合成分的人类BRCA2复合体影响细胞周期进展
L Y Marmorstein1, A V Kinev, G K Chan
1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Cell
|February 24, 2001
概括
研究人员在BRCA2复合体中确定了一个BRCA2-关联因子35 (BRAF35). 这种BRAF35蛋白与凝聚色素结合,并可能调节乳腺癌易感性细胞循环进展.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 人类BRCA2基因的生殖基因突变与乳腺癌风险增加有关.
- 目前尚不完全了解BRCA2蛋白的确切功能.
- 缺少BRCA2的小鼠细胞表现出染色体异常.
研究的目的:
- 为了研究BRCA2蛋白的功能.
- 为了识别BRCA2复合体的组成部分.
- 探索BRCA2在细胞过程中的作用.
主要方法:
- 大型含BRCA2复合体的分离和特征.
- 一个DNA结合元件的识别和分析,BRAF35.
- 在小鼠胚胎中对BRAF35mRNA的表达分析.
- 免疫光染色以评估BRAF35/BRCA2局部化情况.
- 抗体微注射以研究功能性作用.
主要成果:
- 一个2 MDa的BRCA2复合体被分离出来,其中包含一种名为BRAF35.5的DNA结合蛋白.
- BRAF35 具有用于 DNA 结合的 HMG 域和一种类似素的线圈-线圈域.
- BRAF35的mRNA表达反映了BRCA2的表达,在繁殖的胚胎组织中最高.
- 在线分裂过程中,BRAF35/BRCA2复合体与凝结色素局部化.
- 抗体微注射表明该复杂物影响细胞循环的进展.
结论:
- BRAF35是BRCA2复合体的一个新型DNA结合成分.
- BRCA2/BRAF35复合体与染色质相关,可能在细胞循环调节中发挥作用.
- 对BRCA2/BRAF35复合体的进一步研究可以阐明乳腺癌易感性背后的机制.
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