Xu J, Xin S, Du W
Ben May Institute for Cancer Research and Center for Molecular Oncology, University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
FEBS Lett. 2001 Nov 23;508(3):394-8. doi: 10.1016/s0014-5793(01)03103-9.
Chk2 is a major target of ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR). Germline mutations in Chk2 have been identified in a subset of patients with Li-Fraumeni syndrome, suggesting that Chk2 is a tumor suppressor gene. To investigate the role of Chk2 in multicellular organisms, a Drosophila chk2 (Dmchk2) mutant was generated. Dmchk2 mutants are viable but show defects in maintaining genome stability and are highly sensitive to ionizing radiation. Interestingly, mutating Dmchk2 completely blocks DNA damage-induced apoptosis and partially blocks DNA damage-induced cell cycle arrest. These results indicate that Chk2 protein plays a crucial role in the DNA damage response pathway mediating cell cycle arrest and apoptosis, and that the ATM-Chk2 pathway is likely conserved in Drosophila.
Chk2是共济失调毛细血管扩张症突变基因（ATM）以及ATM和Rad3相关蛋白（ATR）的主要作用靶点。在一部分李-佛美尼综合征患者中已发现Chk2的种系突变，这表明Chk2是一种肿瘤抑制基因。为了研究Chk2在多细胞生物中的作用，构建了果蝇chk2（Dmchk2）突变体。Dmchk2突变体能够存活，但在维持基因组稳定性方面存在缺陷，并且对电离辐射高度敏感。有趣的是，使Dmchk2发生突变会完全阻断DNA损伤诱导的细胞凋亡，并部分阻断DNA损伤诱导的细胞周期停滞。这些结果表明，Chk2蛋白在介导细胞周期停滞和细胞凋亡的DNA损伤反应途径中起着关键作用，并且ATM-Chk2途径在果蝇中可能是保守的。
