title: A miR-590/Acvr2a/Rad51b axis regulates DNA damage repair during mESC proliferation.
abstract: Embryonic stem cells (ESCs) enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF), which maintains the self-renewal capability of mouse ESCs (mESCs), significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB) and double-strand break (DSB) damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (Acvr2a) to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR) gene, Rad51b, as a downstream molecule of the miR-590/Acvr2a pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/Acvr2a/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People's Republic of China. Electronic address: jhkang@tongji.edu.cn.
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D020413:3' Untranslated Regions; D030301:Activin Receptors, Type II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051135:Rad51 Recombinase / Q000737:chemistry / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C000602617:MIRN590 microRNA, mouse; D035683:MicroRNAs; C000602618:RAD51B protein, mouse; D012333:RNA, Messenger; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; D051135:Rad51 Recombinase