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Transcriptional activation of short interspersed elements by DNA‐damaging agents
Author(s) -
Rudin Charles M.,
Thompson Craig B.
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1066>3.0.co;2-f
Subject(s) - alu element , biology , transcription (linguistics) , rna polymerase iii , microbiology and biotechnology , reverse transcriptase , human genome , dna , dna replication , dna damage , genetics , dna polymerase , genome , rna , gene , rna polymerase , linguistics , philosophy
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. © 2000 Wiley‐Liss, Inc.