Xu Jinhua, Du Wei
Ben May Institute for Cancer Research and Center for Molecular Oncology, University of Chicago, Chicago, IL 60637, USA.
FEBS Lett. 2003 Jun 19;545(2-3):209-12. doi: 10.1016/s0014-5793(03)00536-2.
Drosophila chk2 (Dmchk2, also called Dmnk) plays a crucial role in the DNA damage response pathway mediating cell cycle arrest and apoptosis [Xu et al., FEBS Lett. 508 (2001) 394-398; Peters et al., Proc. Natl. Acad. Sci. USA 99 (2002) 11305-11310]. In this study, the role of Dmchk2 in early embryogenesis was investigated. In the absence of Dmchk2 function, abnormal nuclei accumulate in the cortex of the syncytial embryo. We show that the abnormal nuclei result from a failure of chromosome segregation probably due to damaged or incomplete replicated DNA. Importantly, this Dmchk2 phenotype is partially suppressed by reducing the gene dosage of polo or stg. As Polo-like kinase was shown to colocalize and coimmunoprecipitate with Chk2 [Tsvetkov et al., J. Biol. Chem. 278 (2003) 8468-8475] in mammals, these observations suggest that polo might be a key target of Dmchk2 in regulating mitotic entry in response to DNA damage or replication block.
果蝇Chk2（Dmchk2，也称为Dmnk）在介导细胞周期停滞和凋亡的DNA损伤反应途径中起着关键作用[Xu等人，《欧洲生物化学学会联合会快报》508（2001）394 - 398；Peters等人，《美国国家科学院院刊》99（2002）11305 - 11310]。在本研究中，研究了Dmchk2在早期胚胎发育中的作用。在缺乏Dmchk2功能的情况下，异常核在合胞体胚胎的皮质中积累。我们表明，异常核是由于染色体分离失败导致的，这可能是由于受损或未完全复制的DNA所致。重要的是，通过降低polo或stg的基因剂量，这种Dmchk2表型得到了部分抑制。由于在哺乳动物中已表明Polo样激酶与Chk2共定位并共免疫沉淀[Tsvetkov等人，《生物化学杂志》278（2003）8468 - 8475]，这些观察结果表明，polo可能是Dmchk2在响应DNA损伤或复制阻滞调节有丝分裂进入过程中的关键靶点。
