Molecular cloning and tissue-specific expression of the mutator2 gene (mu2) in Drosophila melanogaster.

Molecular cloning and tissue-specific expression of the mutator2 gene (mu2) in Drosophila melanogaster.
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果蝇 mutator2 基因 (mu2) 的分子克隆和组织特异性表达。

DOI:
10.1093/genetics/152.3.1025
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发表时间:
1999
期刊:
影响因子:
3.3
通讯作者:
Biessmann,H
Biessmann,H
中科院分区:
生物学2区
文献类型:
--
作者:
Kasravi,A;Walter,MF;Brand,S;Mason,JM;Biessmann,H

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我们在这里提出的果蝇mutator2(mu2)基因的分子克隆和特征,连同其突变表型的进一步遗传分析。μ 2在减数分裂重组期间、成熟卵母细胞中辐射损伤修复期间以及增殖体细胞中的卵子发生中起作用,其中μ 2突变引起体细胞重组的增加。我们的数据表明,mu2代表了一个新的组件在处理双链断裂(DSB)在女性减数分裂。mu2不编码DNA修复酶,因为mu2突变体对DSB诱导剂不过敏。我们已经绘制和克隆了mu2基因,并通过含有mu2基因的基因组DNA片段的种系转化拯救了mu2表型。其cDNA测序表明,mu2编码一种新的139 kD蛋白,这是高度碱性的羧基一半,并携带三个核定位信号和螺旋环螺旋结构域。与性别特异性突变表型一致,该基因在卵巢中表达,但在睾丸中不表达。在卵子发生过程中,它的RNA从滋养细胞迅速转运到卵母细胞中,在卵母细胞中它特异性地积累在前缘。在幼虫体细胞组织的二倍体增殖细胞中表达也很突出。我们的遗传和分子数据与mu2编码卵母细胞核结构成分的模型一致。MU2蛋白可能参与控制染色质结构,因此可能影响DNA双链断裂的加工。
We present here the molecular cloning and characterization of the mutator2 (mu2) gene of Drosophila melanogaster together with further genetic analyses of its mutant phenotype. mu2 functions in oogenesis during meiotic recombination, during repair of radiation damage in mature oocytes, and in proliferating somatic cells, where mu2 mutations cause an increase in somatic recombination. Our data show that mu2 represents a novel component in the processing of double strand breaks (DSBs) in female meiosis. mu2 does not code for a DNA repair enzyme because mu2 mutants are not hypersensitive to DSB-inducing agents. We have mapped and cloned the mu2 gene and rescued the mu2 phenotype by germ-line transformation with genomic DNA fragments containing the mu2 gene. Sequencing its cDNA demonstrates that mu2 encodes a novel 139-kD protein, which is highly basic in the carboxy half and carries three nuclear localization signals and a helix-loop-helix domain. Consistent with the sex-specific mutant phenotype, the gene is expressed in ovaries but not in testes. During oogenesis its RNA is rapidly transported from the nurse cells into the oocyte where it accumulates specifically at the anterior margin. Expression is also prominent in diploid proliferating cells of larval somatic tissues. Our genetic and molecular data are consistent with the model that mu2 encodes a structural component of the oocyte nucleus. The MU2 protein may be involved in controlling chromatin structure and thus may influence the processing of DNA DSBs.