DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA damage via targeting p21/p27.

• Type of Material: Article
• Authors: Bailong Liu, Emory University; Min Liu, Emory University; Jian Wang, Emory University; Xiangming Zhang, Emory University; Xiang Wang, Emory University; Ping Wang, Emory University; Hongyan Wang, Emory University; Wei Li, The First Hospital of Jilin University; Ya Wang, Emory University
• Language: English
• Date: 2015-02-18
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2015.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/nar/gku1368
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 43
• Issue: 3
• Start Page: 1626
• End Page: 1636
• Grant/Funding Information: National Institutes of Health [CA186129 to Y.W. and P30CA138292 to Winship Institute]. Funding for open access charge: National Institutes of Health [CA186129 to Y.W. and P30CA138292 to Winship Institute].
• Research Categories: Health Sciences, Oncology; Health Sciences, Radiology

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.