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

Nucleic Acids Res. 2015 Feb 18;43(3):1626-36. doi: 10.1093/nar/gku1368. Epub 2015 Jan 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Cell Line, Transformed
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology*
  • DNA Damage*
  • G1 Phase
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis*
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Ribonuclease III / physiology*
  • S Phase

Substances

  • CDKN1A protein, human
  • CDKN1B protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • MicroRNAs
  • mirnlet7 microRNA, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases