title: DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA damage via targeting p21/p27.
abstract: Recently, it was reported that knockdown of DICER reduced the ATM-dependent DNA damage response and homologous recombination repair (HRR) via decreasing DICER-generated small RNAs at the damage sites. However, we found that knockdown of DICER dramatically increased cell resistance to camptothecin that induced damage required ATM to facilitate HRR. This phenotype is due to a prolonged G1/S transition via decreasing DICER-dependent biogenesis of miRNA let-7, which increased the p21(Waf1/Cip1)/p27(Kip1) levels and resulted in decreasing the HRR efficiency. These results uncover a novel function of DICER in regulating the cell cycle through miRNA biogenesis, thus affecting cell response to DNA damage.
authors.affiliation: Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Bailong
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cancer Center, The First Hospital of Jilin University, Changchun 130021, China ywang94@emory.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA ywang94@emory.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002461:Cell Line, Transformed; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016196:S Phase
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases