Implication of E3 ligase RAD18 in UV-induced mutagenesis in human induced pluripotent stem cells and neuronal progenitor cells.
Implication of E3 ligase RAD18 in UV-induced mutagenesis in human induced pluripotent stem cells and neuronal progenitor cells.
复制标题
DOI：
10.1093/jrr/rrac099
复制
发表时间：
2023-03-23
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
多能干细胞（PSC）具有分化为任何其他器官的潜力。PSC的基因组DNA完整性通过参与DNA修复、细胞周期和凋亡的许多基因的高水平转录来维持。然而，目前尚不清楚基因突变的频率有多高，以及这些DNA修复因子在PSC中如何发挥作用。在这项研究中，我们采用Sup F分析来测量作为PSC模型的诱导多能干细胞（iPSC）在UV-C照射后的突变频率，并且神经祖细胞（NPC）作为分化的细胞来源于iPSC。与原始皮肤成纤维细胞相比，iPSC和NPC表现出较低的突变频率。在RNA-seq分析中，iPSC和NPC显示出高表达的RAD 18，其在DNA复制过程中参与紧急耐受系统的跨损伤合成（TLS）。尽管RAD 18参与体细胞中的无错和易错TLS，但RAD 18在PSC中的功能仍然未知。在这项研究中，我们通过siRNA敲低耗尽了RAD 18，导致iPSC和NPC中突变频率降低。我们的研究结果将提供PSC基因组维护机制的信息。
Pluripotent stem cells (PSCs) have the potential to differentiate to any of the other organs. The genome DNA integrity of PSCs is maintained by a high level of transcription for a number of genes involved in DNA repair, cell cycle and apoptosis. However, it remains unclear how high the frequency of genetic mutation is and how these DNA repair factors function in PSCs. In this study, we employed Sup F assay for the measurement of mutation frequency after UV-C irradiation in induced pluripotent stem cells (iPSCs) as PSC models and neural progenitor cells (NPCs) were derived from iPSCs as differentiated cells. iPSCs and NPCs exhibited a lower mutation frequency compared with the original skin fibroblasts. In RNA-seq analysis, iPSCs and NPCs showed a high expression of RAD18, which is involved in trans-lesion synthesis (TLS) for the emergency tolerance system during the replication process of DNA. Although RAD18 is involved in both error free and error prone TLS in somatic cells, it still remains unknown the function of RAD18 in PSCs. In this study we depleted of the RAD18 by siRNA knockdown resulted in decreased frequency of mutation in iPSCs and NPCs. Our results will provide information on the genome maintenance machinery in PSCs.
登录
查看更多内容
影响因子：
5.9
作者：
Nori, Satoshi;Okada, Yohei;Nishimura, Soraya;Sasaki, Takashi;Itakura, Go;Kobayashi, Yoshiomi;Renault-Mihara, Francois;Shimizu, Atsushi;Koya, Ikuko;Yoshida, Rei;Kudoh, Jun;Koike, Masato;Uchiyama, Yasuo;Ikeda, Eiji;Toyama, Yoshiaki;Nakamura, Masaya;Okano, Hideyuki
通讯作者：
Okano, Hideyuki
影响因子：
25
作者：
Suberbielle, Elsa;Sanchez, Pascal E.;Kravitz, Alexxai V.;Wang, Xin;Ho, Kaitlyn;Eilertson, Kirsten;Devidze, Nino;Kreitzer, Anatol C.;Mucke, Lennart
通讯作者：
Mucke, Lennart
影响因子：
3.5
作者：
PARRIS, CN;SEIDMAN, MM
通讯作者：
SEIDMAN, MM
DOI：
10.1016/j.ijrobp.2019.05.006
发表时间：
2019-09-01
影响因子：
7
作者：
Miyake, Tomoko;Shimada, Mikio;Okino, Akitoshi
通讯作者：
Okino, Akitoshi
RAD18 传递 DNA 损伤信号以引发同源重组修复。
影响因子：
21.3
作者：
Huang, Jun;Huen, Michael S. Y.;Kim, Hongtae;Leung, Charles Chung Yun;Glover, J. N. Mark;Yu, Xiaochun;Chen, Junjie
通讯作者：
Chen, Junjie