Positional analyses of BRCA1-dependent expression in Saccharomyces cerevisiae.
Positional analyses of BRCA1-dependent expression in Saccharomyces cerevisiae.
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DOI：
10.4161/cc.7.24.7380
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Eastman L
中科院分区：
文献类型：
--
作者：
Skibbens RV;Ringhoff DN;Marzillier J;Cassimeris L;Eastman L
BRCA1突变在遗传性乳腺癌和卵巢癌中占很大比例，但对BRCA1功能的分析因其多效性和结合伙伴（Pol II全酶和转录因子、染色质重塑物、重组复合物和E3连接酶）而变得复杂。在脊椎动物细胞中，阐明BRCA1转录效应的努力主要集中在特定基因或限制性部分，基因组限制分析BRCA1对相邻DNA序列和染色体长度的影响。在这里，我们使用微阵列分析遗传易处理的酵母细胞系统来阐明brca1依赖的全基因组定位效应对基因诱导和抑制。基于BRCA1严重降低酵母生长动力学的发现，酵母反应可能具有临床相关性，但BRCA1在乳腺肿瘤中发现的位点突变不再能够延缓酵母细胞生长动力学。我们的分析表明，BRCA1通过转录因子上调特定位点和染色质重塑复合物，从而影响基因表达的全局变化。BRCA1也表现出基因抑制活性。聚类功能分析表明，这些抑制因子是有丝分裂稳定性所必需的，并为BRCA1和染色体分离基因之间观察到的条件致死性提供了新的分子解释。
Mutations in BRCA1 account for a significant proportion of hereditary breast and ovarian cancers, but analysis of BRCA1 function is complicated by pleiotropic effects and binding partners (Pol II holoenzyme and transcription factors, chromatin remodelers, recombination complexes and E3 ligases). In vertebrate cells, efforts to elucidate BRCA1 transcriptional effects have focused on specific genes or restricted portions of the genome—limiting analyses of BRCA1 effects on adjoining DNA sequences and along chromosome lengths. Here, we use microarray analyses on the genetically tractable yeast cell system to elucidate BRCA1-dependent genome-wide positional effects on both gene induction and repression. Yeast responses may be of clinical relevance based on findings that BRCA1 severely diminishes yeast growth kinetics but that BRCA1 mutated at sites identified from breast tumors is no longer able to retard yeast cell growth kinetics. Our analysis suggests that BRCA1 acts through both transcription factors to upregulate specific loci and chromatin remodeling complexes to effect global changes in gene expression. BRCA1 also exhibits gene repression activities. Cluster-functional analysis reveals that these repressed factors are required for mitotic stability and provide a novel molecular explanation for the conditional lethality observed between BRCA1 and chromosome segregation genes.
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影响因子：
4.3
作者：
Bae, I;Rih, JK;Rosen, EM
通讯作者：
Rosen, EM
DOI：
10.1073/pnas.94.11.5820
发表时间：
1997-05-27
影响因子：
11.1
作者：
Humphrey, JS;Salim, A;Klausner, RD
通讯作者：
Klausner, RD
BRCA1连接乳腺癌中雌激素受体α缺乏症的分子基础。
DOI：
10.1093/jnci/djm207
发表时间：
2007-11-21
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Hosey AM;Gorski JJ;Murray MM;Quinn JE;Chung WY;Stewart GE;James CR;Farragher SM;Mulligan JM;Scott AN;Dervan PA;Johnston PG;Couch FJ;Daly PA;Kay E;McCann A;Mullan PB;Harkin DP
通讯作者：
Harkin DP
DOI：
10.1083/jcb.145.1.15
发表时间：
1999-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hyland KM;Kingsbury J;Koshland D;Hieter P
通讯作者：
Hieter P
影响因子：
3.6
作者：
Coyne, RS;McDonald, HB;Brody, LC
通讯作者：
Brody, LC