Transcriptional activation of short interspersed elements by DNA-damaging agents

Charles M. Rudin, Craig B. Thompson

Research output: Contribution to journalArticle

Abstract

Short interspersed elements (SINEs), typified by the human Alu repeat, are RNA polymerase III (pol III)-transcribed sequences that replicate within the genome through an RNA intermediate. Replication of SINEs has been extensive in mammalian evolution: an estimated 5% of the human genome consists of Alu repeats. The mechanisms regulating transcription, reverse transcription, and reinsertion of SINE elements in genomic DNA are poorly understood. Here we report that expression of murine SINE transcripts of both the B1 and B2 classes is strongly upregulated after prolonged exposure to cisplatin, etoposide, or gamma radiation. A similar induction of Alu transcripts in human cells occurs under these conditions. This induction is not due to a general upregulation of pol III activity in either species. Genotoxic treatment of murine cells containing an exogenous human Alu element induced Alu transcription. Concomitant with the increased expression of SINEs, an increase in cellular reverse transcriptase was observed after exposure to these same DNA-damaging agents. These findings suggest that genomic damage may be an important activator of SINEs, and that SINE mobility may contribute to secondary malignancy after exposure to DNA-damaging chemotherapy. (C) 2001 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalGenes Chromosomes and Cancer
Volume30
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

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Transcriptional Activation
DNA
Alu Elements
RNA Polymerase III
RNA-Directed DNA Polymerase
Gamma Rays
Human Genome
Etoposide
Cisplatin
Reverse Transcription
Up-Regulation
Genome
RNA
Drug Therapy
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Transcriptional activation of short interspersed elements by DNA-damaging agents. / Rudin, Charles M.; Thompson, Craig B.

In: Genes Chromosomes and Cancer, Vol. 30, No. 1, 2001, p. 64-71.

Research output: Contribution to journalArticle

Rudin, Charles M. ; Thompson, Craig B. / Transcriptional activation of short interspersed elements by DNA-damaging agents. In: Genes Chromosomes and Cancer. 2001 ; Vol. 30, No. 1. pp. 64-71.
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