Induction of serl5 and 1ys382 modifications of p53 by blockage of transcription elongation

Mats Ljungman, Heather O'Hagan, Michelle T. Paulsen

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Blockage of transcription has been shown to induce the tumor suppressor p53 in human cells. We here show that RNA synthesis inhibitors blocking the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II, such as DRB and H7, induced rapid nuclear accumulation of p53 proteins that were not phosphorylated at serl5 or acetylated at lys382. In contrast, agents that inhibit the elongation phase of transcription, such as UV light, camptothecin or actinomycin D, induced the accumulation of nuclear p53 proteins that were modified at both of these sites. Furthermore, using a panel of DNA repair-deficient cells we show that persistent DNA lesions in the transcribed strand of active genes are responsible for the induction of the serl5 and 1ys382 modifications following UV-irradiation. We conclude that inhibition of transcription is sufficient for the accumulation of p53 in the nucleus regardless of whether the serl5 site of p53 is phosphorylated or not. Importantly, blockage of the elongation phase of transcription triggers a distinct signaling pathway leading to p53 modifications on serl5 and 1ys382. We propose that the elongating RNA polymerase complex may act as a sensor of DNA damage and as an integrator of cellular stress signals.

Original languageEnglish (US)
Pages (from-to)5964-5971
Number of pages8
JournalOncogene
Volume20
Issue number42
DOIs
StatePublished - Sep 20 2001
Externally publishedYes

Fingerprint

DNA Repair-Deficiency Disorders
Dichlororibofuranosylbenzimidazole
Nucleic Acid Synthesis Inhibitors
Camptothecin
RNA Polymerase II
Dactinomycin
DNA-Directed RNA Polymerases
Ultraviolet Rays
Nuclear Proteins
DNA Damage
Phosphorylation
DNA
Genes
Neoplasms
Proteins

Keywords

  • Cockayne's syndrome
  • DNA damage
  • Inhibitors
  • RNA polymerase II
  • UV light
  • Xeroderma pigmentosum

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Induction of serl5 and 1ys382 modifications of p53 by blockage of transcription elongation. / Ljungman, Mats; O'Hagan, Heather; Paulsen, Michelle T.

In: Oncogene, Vol. 20, No. 42, 20.09.2001, p. 5964-5971.

Research output: Contribution to journalArticle

Ljungman, Mats ; O'Hagan, Heather ; Paulsen, Michelle T. / Induction of serl5 and 1ys382 modifications of p53 by blockage of transcription elongation. In: Oncogene. 2001 ; Vol. 20, No. 42. pp. 5964-5971.
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