Drosophila homologue of the Rothmund-Thomson syndrome gene: essential function in DNA replication during development.
Drosophila homologue of the Rothmund-Thomson syndrome gene: essential function in DNA replication during development.
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DOI：
10.1016/j.ydbio.2008.08.006
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发表时间：
2008-11-01
影响因子：
2.7
通讯作者：
Hsieh, Tao-shih
中科院分区：
文献类型：
--
作者：
Wu, Jianhong;Capp, Christopher;Feng, Liping;Hsieh, Tao-shih
RecQ家族成员在维持基因组完整性方面发挥着关键作用。人类RecQL 4突变导致一种罕见的遗传疾病，Rothmund-Thomson综合征。转基因小鼠实验表明RecQ 4无效突变体导致胚胎死亡。虽然生化证据表明，非洲爪蟾RecQ 4是卵母细胞提取物中DNA复制的起始所必需的，但其在发育过程中的生物学功能仍有待阐明。我们在这里提出我们的结果，建立使用果蝇作为一个模型系统，以探测RecQ 4的功能。监测RecQ 4的细胞分布的免疫荧光实验表明，RecQ 4表达在S期达到峰值，并且RecQ 4仅在DNA复制活跃的组织中表达，而不在静止细胞中表达。我们已经分离出果蝇RecQ 4亚型突变体recqEP和recq 423，它们特异性地将卵泡细胞的绒毛膜基因扩增减少4-5倍，导致蛋壳薄而脆弱，以及雌性不育。对绒毛膜基因簇中14 kb区域扩增缺陷的定量分析表明，RecQ 4可能在复制起点或其附近具有特异性功能。无效等位基因recq 419导致细胞增殖失败、DNA复制减少、染色体断裂和在第一龄幼虫阶段的致死性。嵌合体分析表明具有纯合recq 419的细胞克隆不能增殖。这些结果表明，RecQ 4对生存力和生育力至关重要，并且在发育过程中DNA复制的大多数方面都是必需的。
Members of the RecQ family play critical roles in maintaining genome integrity. Mutations in human RecQL4 cause a rare genetic disorder, Rothmund-Thomson syndrome. Transgenic mice experiments showed that the RecQ4 null mutant causes embryonic lethality. Although biochemical evidence suggests that the Xenopus RecQ4 is required for the initiation of DNA replication in the oocyte extract, its biological functions during development remain to be elucidated. We present here our results in establishing the use of Drosophila as a model system to probe RecQ4 functions. Immunofluorescence experiments monitoring the cellular distribution of RecQ4 demonstrated that RecQ4 expression peaks during S phase, and RecQ4 is expressed only in tissues active in DNA replication, but not in quiescent cells. We have isolated Drosophila RecQ4 hypomorphic mutants, recqEP and recq423, which specifically reduce chorion gene amplification of follicle cells by 4–5 fold, resulting in thin and fragile eggshells, and female sterility. Quantitative analysis on amplification defects over a 14-kb domain in chorion gene cluster suggests that RecQ4 may have a specific function at or near the origin of replication. A null allele recq419 causes a failure in cell proliferation, decrease in DNA replication, chromosomal fragmentation, and lethality at the stage of first instar larvae. The mosaic analysis indicates that cell clones with homozygous recq419 fail to proliferate. These results indicate that RecQ4 is essential for viability and fertility, and is required for most aspects of DNA replication during development.
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影响因子：
2.7
作者：
BRYANT, PJ;LEVINSON, P
通讯作者：
LEVINSON, P
影响因子：
56.9
作者：
Kusano, K;Johnson-Schlitz, DM;Engels, WR
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Engels, WR
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4.4
作者：
Kitao, S;Ohsugi, I;Shimamoto, A
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Shimamoto, A
影响因子：
14.9
作者：
Drysdale RA;Crosby MA;FlyBase Consortium
通讯作者：
FlyBase Consortium
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9.7
作者：
Larizza, L;Magnani, I;Roversi, G
通讯作者：
Roversi, G