Mre11-Rad50-Nbs complex is required to cap telomeres during Drosophila embryogenesis
Mre11-Rad50-Nbs complex is required to cap telomeres during Drosophila embryogenesis
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DOI：
10.1073/pnas.0902707106
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发表时间：
2009-06-30
影响因子：
11.1
通讯作者：
Rong, Yikang S.
中科院分区：
文献类型：
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作者：
Gao, Guanjun;Bi, Xiaolin;Rong, Yikang S.
以果蝇为模型系统，我们发现在早期胚胎发育过程中，端粒保护对Mre11-Rad50-Nbs （MRN）功能有严格的要求。在mre11或nbs中发生半胚突变的纯合动物发育正常，端粒功能障碍最小。然而，它们产生的胚胎由于端粒DNA的共价融合导致有丝分裂失败而无法存活。有趣的是，分子缺陷不是缺乏MRN相互作用或Mre11核酸酶活性，而是这些胚胎中母体Nbs蛋白池的耗尽。由于Nbs的缺失，Mre11和Rad50 （MR）被排除在染色质之外。果蝇的母体效应致死率与在人类患者中发现的携带亚形态mrn突变的小鼠相似，这表明由于mrn完整性的丧失，端粒维持存在共同缺陷。
Using Drosophila as a model system, we identified here a stringent requirement for Mre11-Rad50-Nbs (MRN) function in telomere protection during early embryonic development. Animals homozygous for hypomorphic mutations in either mre11 or nbs develop normally with minimal telomere dysfunction. However, they produce inviable embryos that succumb to failure of mitosis caused by covalent fusion of telomeric DNA. Interestingly, the molecular defect is not the absence of MRN interaction or of Mre11 nuclease activities, but the depletion of the maternal pool of Nbs protein in these embryos. Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. This maternal effect lethality in Drosophila is similar to that seen in mice carrying hypomorphic mrn mutations found in human patients, suggesting a common defect in telomere maintenance because of the loss of MRN integrity.