AIMP3 Deletion Induces Acute Radiation Syndrome-like Phenotype in Mice.
AIMP3 Deletion Induces Acute Radiation Syndrome-like Phenotype in Mice.
复制标题
DOI：
10.1038/s41598-018-33303-3
复制
发表时间：
2018-10-09
影响因子：
4.6
通讯作者：
Kim S
中科院分区：
文献类型：
--
作者：
Kim D;Kim S;Oh Y;Park S;Jeon Y;Kim H;Lee H;Kim S
基因组大多受到保护，不受内部或外部持续的DNA破坏威胁的影响，这些威胁最终维持了生物体。在此，我们报告说，AIMP3，以前证明的肿瘤抑制因子，在维持成年小鼠基因组的完整性中起着至关重要的作用。在成年小鼠中通过他莫昔芬诱导AIMP3的暂时系统性缺失后，动物发展出急性放射综合征样表型，其典型表现为硬皮病、造血细胞和器官的萎缩以及肠衰竭。在脾、肠和高度复制的胚胎皮层中观察到γH2AX的诱导，γ H2AX是DNA双链断裂的早期标记。此外，AIMP3 mKO小鼠的亚致死辐射显著影响器官损伤和存活。使用从条件KO小鼠或AIMP3敲低细胞中分离的MEFs，我们通过COMET测定和γH2AX诱导证实了自发发生的DNA双链断裂的存在。此外，γH2AX的去除被延迟，同源DNA修复活性显著降低。RPA焦点形成的减少和随后的Rad51焦点形成可能是在AIMP3不存在下同源重组活性显著降低的基础。总之，我们的数据表明，AIMP3通过DNA修复过程在基因组稳定性中发挥作用。
Genomes are mostly protected from constant DNA-damaging threats, either internal or external, which ultimately sustain the organism. Herein, we report that AIMP3, a previously demonstrated tumour suppressor, plays an essential role in maintaining genome integrity in adult mice. Upon induction of the temporal systemic deletion of AIMP3 by tamoxifen in adult mice, the animals developed an acute radiation syndrome-like phenotype, typified by scleroderma, hypotrophy of haematopoietic cells and organs, and intestinal failure. Induction of γH2AX, an early marker of DNA double-strand breaks, was observed in the spleen, intestine, and the highly replicating embryonic cortex. In addition, sub-lethal irradiation of AIMP3 mKO mice dramatically affected organ damage and survival. Using isolated MEFs from conditional KO mice or AIMP3 knockdown cells, we confirmed the presence of spontaneously occurring DNA double-strand breaks by COMET assay and γH2AX induction. Furthermore, γH2AX removal was delayed, and homologous DNA repair activity was significantly reduced. Reduction of RPA foci formation and subsequent Rad51 foci formation probably underlie the significant reduction in homologous recombination activity in the absence of AIMP3. Together, our data demonstrate that AIMP3 plays a role in genome stability through the DNA repair process.
登录
查看更多内容
影响因子：
16.6
作者：
Husain A;Begum NA;Taniguchi T;Taniguchi H;Kobayashi M;Honjo T
通讯作者：
Honjo T
影响因子：
4.5
作者：
Keyamura K;Arai K;Hishida T
通讯作者：
Hishida T
影响因子：
4.8
作者：
Cho, Ha Yeon;Maeng, Seo Jin;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
14.8
作者：
Olive, Peggy L.;Banath, Judit P.
通讯作者：
Banath, Judit P.
多合成酶复合体基因的遗传变异与中国人群的 DNA 损伤水平相关
DOI：
10.1016/j.mrfmmm.2016.01.006
发表时间：
2016-04-01
影响因子：
2.3
作者：
Liu, Jia;Zhu, Meng;Shen, Hongbing
通讯作者：
Shen, Hongbing