Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity
Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity
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DOI：
10.1016/s0092-8674(03)00202-2
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发表时间：
2003-04-04
期刊：
影响因子：
64.5
通讯作者：
Theurkauf, WE
中科院分区：
文献类型：
--
作者：
Takada, S;Kelkar, A;Theurkauf, WE
在合胞体果蝇胚胎中，受损或不完全复制的DNA在有丝分裂中触发中心体破坏，导致纺锤体组装缺陷和后期染色体分离。受损的细胞核从皮层脱落，并没有被整合到形成胚胎的细胞中。果蝇检查点激酶2肿瘤抑制因子同源物[DmChk 2]中的无效突变阻断了这种对DNA损伤的有丝分裂反应，并且还防止了有缺陷的细胞核从皮质的丢失。此外，DNA损伤导致DmChk2定位于中心体和纺锤体微管的增加。因此，DmChk2是必不可少的“有丝分裂灾难”的信号，破坏中心体功能，以响应遗传毒性的压力，并确保突变体和非整倍体细胞核从胚胎前体池中消除。
In syncytial Drosophila embryos, damaged or incompletely replicated DNA triggers centrosome disruption in mitosis, leading to defects in spindle assembly and anaphase chromosome segregation. The damaged nuclei drop from the cortex and are not incorporated into the cells that form the embryo proper. A null mutation in the Drosophila checkpoint kinase 2 tumor suppressor homolog [DmChk2) blocks this mitotic response to DNA lesions and also prevents loss of defective nuclei from the cortex. In addition, DNA damage leads to increased DmChk2 localization to the centrosome and spindle microtubules. DmChk2 is therefore essential for a "mitotic catastrophe" signal that disrupts centrosome function in response to genotoxic stress and ensures that mutant and aneuploid nuclei are eliminated from the embryonic precursor pool.