Tumor suppressor p53 represses transcription of RECQ4 helicase

Sagar Sengupta, Akira Shimamoto, Minori Koshiji, Remy Pedeux, Marek Rusin, Elisa A. Spillare, Jiang Cheng Shen, L. Eric Huang, Noralane M. Lindor, Yasuhiro Furuichi, Curtis C. Harris

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

RECQ4 is a member of the RecQ helicase family, which has been implicated in the regulation of DNA replication, recombination and repair. p53 modulates the functions of RecQ helicases including BLM and WRN. In this study, we demonstrate that p53 can regulate the transcription of RECQ4. Using nontransformed, immortalized normal human fibroblasts, we show that p53-dependent down-regulation of RECQ4 expression occurred in G1-arrested cells, both in the absence or presence of exogenous DNA damage. Wild-type p53 (but not the tumor-derived mutant forms) repressed RECQ4 promoter activity. The camptothecin or etoposide-dependent p53-mediated repression was attenuated by trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs). Repression of the RECQ4 promoter was accompanied with an increased accumulation of HDAC1, and the loss of SP1 and p53 binding to the promoter. The simultaneous formation of a camptothecin-dependent p53-SP1 complex indicated its occurrence outside of the RECQ4 promoter. These data suggest that p53-mediated repression of RECQ4 transcription during DNA damage results from the modulation of the promoter occupancy of transcription activators and repressors.

Original languageEnglish (US)
Pages (from-to)1738-1748
Number of pages11
JournalOncogene
Volume24
Issue number10
DOIs
StatePublished - Mar 3 2005

Keywords

  • Histone deacetylases
  • Promoter
  • Repression
  • Rothmund-Thomson syndrome
  • SP1
  • Trichostatin A

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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