Tumor suppressor p53 represses transcription of RECQ4 helicase.
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 downregulation 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.
Sengupta
Sagar
S
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shimamoto
Akira
A
Koshiji
Minori
M
Pedeux
Remy
R
Rusin
Marek
M
Spillare
Elisa A
EA
Shen
Jiang Cheng
JC
Huang
L Eric
LE
Lindor
Noralane M
NM
Furuichi
Yasuhiro
Y
Harris
Curtis C
CC
D002478:Cells, Cultured; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics*; D016193:G1 Phase; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D053484:RecQ Helicases; D012097:Repressor Proteins / Q000502:physiology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D006877:Hydroxamic Acids; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C012589:trichostatin A; D006655:Histone Deacetylases; D004265:DNA Helicases; D053484:RecQ Helicases