Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response
Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response
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DOI：
10.1093/emboj/cdg543
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发表时间：
2003-10-15
期刊：
影响因子：
11.4
通讯作者：
Cagan, RL
中科院分区：
文献类型：
--
作者：
Jassim, OW;Fink, JL;Cagan, RL
紫外线被细胞蛋白质和DNA吸收，促进皮肤损伤、衰老和癌症。在本文中，我们探讨了果蝇视网膜细胞对紫外线的反应。我们证明视网膜在幼虫发育过程中进入紫外线敏感期，这一时期与正常发育的程序性细胞死亡密切相关。辐射对细胞的损伤包括细胞形态的改变和细胞的凋亡，这些缺陷完全可以由DNA损伤来解释。Caspase抑制剂P35可以阻止细胞死亡，但不能阻止细胞形态的改变。利用遗传和微阵列数据，我们为HID表达的中心作用和Diap1蛋白在控制紫外线反应中的稳定性提供了证据。相反，我们发现收割机对紫外线敏感性没有影响。令人惊讶的是，Dmp53是保护细胞免受紫外线介导的细胞死亡所必需的，这一效果归因于它在DNA修复中的作用。这些体内结果表明，DNA损伤的细胞效应取决于组织的发育状态。
Ultraviolet (UV) light is absorbed by cellular proteins and DNA, promoting skin damage, aging and cancer. In this paper, we explore the UV response by cells of the Drosophila retina. We demonstrate that the retina enters a period of heightened UV sensitivity in the young developing pupa, a stage closely associated with its period of normal developmental programmed cell death. Injury to irradiated cells included morphology changes and apoptotic cell death; these defects could be completely accounted for by DNA damage. Cell death, but not morphological changes, was blocked by the caspase inhibitor P35. Utilizing genetic and microarray data, we provide evidence for the central role of Hid expression and for Diap1 protein stability in controlling the UV response. In contrast, we found that Reaper had no effect on UV sensitivity. Surprisingly, Dmp53 is required to protect cells from UV-mediated cell death, an effect attributed to its role in DNA repair. These in vivo results demonstrate that the cellular effects of DNA damage depend on the developmental status of the tissue.