RMI1 attenuates tumor development and is essential for early embryonic survival.
RMI1 attenuates tumor development and is essential for early embryonic survival.
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DOI：
10.1002/mc.20694
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发表时间：
2011-02
影响因子：
4.6
通讯作者：
Li, L.
中科院分区：
文献类型：
--
作者：
Chen, H.;You, M. J.;Jiang, Y.;Wang, W.;Li, L.
RMI1/BLAP75(RecQ介导的基因组不稳定1/Bloom相关蛋白75)是从酵母到人类高度保守的OB折叠蛋白。以往的研究表明，RMI1对BLm/RMI1/TopIIIα复合体的稳定性和抑制升高的姐妹染色单体交换(姐妹染色单体交换)是必需的。在体外，RMI1的存在强烈刺激Bloom解旋酶的Holliday溶解活性。然而，RMI1的体内功能在很大程度上仍未确定。为了解决这个问题，我们通过同源替换靶向获得了RMI1基因敲除小鼠。我们发现，虽然RMI1+/−小鼠没有表现出明显的发育表型，但两个mRMI1等位基因的缺失都会导致胚胎在着床前早期死亡。为了确定RMI1是否在肿瘤发生中发挥作用，我们建立了RMI1/P53双重杂合子小鼠，并分析了它们在电离辐射诱导的肿瘤发展中的开始。与野生型Rmi+/−和P53+/−小鼠相比，Rmi+/−/P53+/−小鼠死于肿瘤的频率更高，生存时间显著缩短。这些结果证实了RMI1在胚胎发育和肿瘤抑制中的双重作用。
RMI1/BLAP75 (RecQ-Mediated Genome Instability 1/Bloom Associated protein 75) is an OB-fold protein highly conserved from yeast to human. Previous studies showed that RMI1 is required for the stability of the BLM/RMI1/TopIIIα complex and for the suppression of elevated sister chromatids exchange (SCE). The presence of RMI1 strongly stimulates the Holliday dissolution activity of the Bloom helicase in vitro. The in vivo function of RMI1, however, remains largely undefined. To address this question, we generated RMI1 knockout mice through homologous replacement targeting. We found that, while RMI1+/− mice showed no obvious developmental phenotype, deletion of both mRMI1 alleles resulted in early embryonic lethality before implantation. To determine whether RMI1 plays a role in tumorigenesis, we generated RMI1/p53 double heterozygous mice and analyzed their onset of ionizing radiation-induced tumor development. RMI1+/−/p53+/− mice succumbed to tumor with a higher frequency and exhibited a substantially shortened survival when compared to the wild type, RMI1+/− and p53+/− cohorts. These results demonstrated a dual-role of RMI1 in embryonic development and tumor suppression.
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