Mutations in the BRCT domain confer temperature sensitivity to BRCA1 in transcription activation
Mutations in the BRCT domain confer temperature sensitivity to BRCA1 in transcription activation
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DOI：
10.4161/cbt.1.5.165
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发表时间：
2002-09-01
影响因子：
3.6
通讯作者：
Monteiro, ANA
中科院分区：
文献类型：
--
作者：
Carvalho, MA;Billack, B;Monteiro, ANA
BRCA 1是一种肿瘤抑制基因，生殖系突变占乳腺癌和卵巢癌家族病例的大多数。越来越多的证据表明BRCA 1在DNA修复和转录调控中发挥作用。剖析BRCA 1作用的一个主要障碍是缺乏进行生化和遗传实验的分子试剂。因此，我们使用随机突变的C-末端的BRCA 1（aa 1560-1863），以产生温度敏感（TS）突变体的转录激活。我们在转录中获得了IITS突变体，其主要定位于BRCA 1的BRCT-N结构域的疏水核心。其中一个突变体H1686 Q在人类细胞中也显示出温度依赖性转录激活。这些条件突变体代表了评估BRCA 1在转录激活中的作用的有价值的工具。
BRCA1 is a tumor suppressor gene and germ line mutations account for the majority of familial cases of breast and ovarian cancer. There is mounting evidence that BRCA1 functions in DNA repair and transcriptional regulation. A major hurdle to dissect the role of BRCA1 is the lack of molecular reagents to carry out biochemical and genetic experiments. Therefore, we used random mutagenesis of the C-terminus of BRCA1 (aa 1560-1863) to generate temperature-sensitive (TS) mutants in transcription activation. We obtained I I TS mutants in transcription that localized primarily to the hydrophobic core of the BRCT-N domain of BRCA1. One of the mutants, H1686Q, also displayed temperature-dependent transcription activation in human cells. These conditional mutants represent valuable tools to assess the role of BRCA1 in transcription activation.