BRCA1 is a component of the RNA polymerase II holoenzyme
BRCA1 is a component of the RNA polymerase II holoenzyme
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DOI：
10.1073/pnas.94.11.5605
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发表时间：
1997-05-27
影响因子：
11.1
通讯作者：
Parvin, JD
中科院分区：
文献类型：
--
作者：
Scully, R;Anderson, SF;Parvin, JD
家族性乳腺-卵巢肿瘤抑制基因产物BRCA1通过多个标准被发现是RNA聚合酶II全酶的一个组成部分，通过多个色谱步骤发现BRCA1与全酶共硫化。其他被测试的转录激活剂可能潜在地与全酶接触，但与全酶的关系不稳定，这是通过共凝固来确定的。针对全酶组分hSRB7的抗体特异性纯化BRCA1， BRCA1复合物的免疫纯化也特异性纯化转录活性RNA聚合酶II和转录因子TFIIF、TFIIE和TFIIH。此外，在约90%的临床相关突变中缺失的BRCA1结构域参与了细胞中与全酶复合物的结合。这些数据与最近的数据一致，这些数据确定了BRCA1蛋白中的转录激活域，并将BRCA1肿瘤抑制蛋白作为全酶结合蛋白与转录过程联系起来。
The familial breast-ovarian tumor suppressor gene product BRCA1 was found to be a component of the RNA polymerase II holoenzyme by several criteria, BRCA1 was found to copurify with the holoenzyme over multiple chromatographic steps. Other tested transcription activators that could potentially contact the holoenzyme were not stably associated with the holoenzyme as determined by copurification. Antibody specific for the holoenzyme component hSRB7 specifically purifies BRCA1, Immunopurification of BRCA1 complexes also specifically purifies transcriptionally active RNA polymerase II and transcription factors TFIIF, TFIIE, and TFIIH. Moreover, a BRCA1 domain, which is deleted in about 90% of clinically relevant mutations, participates in binding to the holoenzyme complex in cells. These data are consistent with recent data identifying transcription activation domains in the BRCA1 protein and link the BRCA1 tumor suppressor protein with the transcription process as a holoenzyme-bound protein.