Sea urchin embryo as a model for analysis of the signaling pathways linking DNA damage checkpoint, DNA repair and apoptosis
Sea urchin embryo as a model for analysis of the signaling pathways linking DNA damage checkpoint, DNA repair and apoptosis
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DOI：
10.1007/s00018-007-7173-0
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发表时间：
2007-07-01
影响因子：
8
通讯作者：
Mulner-Lorillon, O.
中科院分区：
文献类型：
--
作者：
Le Bouffant, R.;Cormier, P.;Mulner-Lorillon, O.
对海胆早期胚胎的DNA完整性检查点控制进行了研究。用甲基磺酸甲酯(MMS)或博莱霉素等遗传毒性物质处理胚胎，可诱导细胞周期检查点的激活，表现为胚胎分裂延迟或停止，并抑制CDK1/Cyclin B激活的去磷酸化。遗传毒性处理可引起DNA损伤，其损伤程度与遗传毒性浓度有关，并与观察到的细胞周期延迟有关。在低遗传毒性浓度下，胚胎能够修复DNA损伤并从检查点停滞中恢复，而在高剂量下，胚胎经历了以细胞凋亡为特征的形态和生化变化。最后，从胚胎中提取的提取物在与模拟损伤的寡核苷酸孵育后，被发现能够支持体外DNA修复。综上所述，我们的结果表明，海胆早期胚胎包含完全功能和可激活的DNA损伤检查点。海胆胚胎被认为是研究细胞周期检查点、DNA修复和细胞凋亡信号通路的一个很有前途的模型，这些信号通路在解除调控后在癌症的起源中发挥着重要作用。
DNA integrity checkpoint control was studied in the sea urchin early embryo. Treatment of the embryos with genotoxic agents such as methyl methanesulfonate (MMS) or bleomycin induced the activation of a cell cycle checkpoint as evidenced by the occurrence of a delay or an arrest in the division of the embryos and an inhibition of CDK1/cyclin B activating dephosphorylation. The genotoxic treatment was shown to induce DNA damage that depended on the genotoxic concentration and was correlated with the observed cell cycle delay. At low genotoxic concentrations, embryos were able to repair the DNA damage and recover from checkpoint arrest, whereas at high doses they underwent morphological and biochemical changes characteristic of apoptosis. Finally, extracts prepared from embryos were found to be capable of supporting DNA repair in vitro upon incubation with oligonucleotides mimicking damage. Taken together, our results demonstrate that sea urchin early embryos contain fully functional and activatable DNA damage checkpoints. Sea urchin embryos are discussed as a promising model to study the signaling pathways of cell cycle checkpoint, DNA repair and apoptosis, which upon deregulation play a significant role in the origin of cancer.