Transcription and DNA damage

A link to a kink

David A. Scicchitano, Isabel Mellon

Research output: Contribution to journalArticle

Abstract

Living organisms are constantly exposed to a variety of naturally occurring and man-made chemical and physical agents that pose threats to health by causing cancer and other illnesses, as well as cell death. One mechanism by which these moieties can exert their toxic effects is by inducing modifications to the genome. Such changes in DNA often result in the formation of nucleotides not normally found in the double helix, bases containing covalent chemical alterations, single- and double-strand breaks, and interstrand and intrastrand cross-links. When these lesions are present during replication, mutations often result in the newly synthesized DNA. Likewise, when such damage occurs in a gene, transcription elongation, and hence expression, can be adversely affected because of pausing or arresting of the RNA polymerase at or near the altered site; this could result in the synthesis of a defective RNA molecule. It has become increasingly clear that transcription and DNA damage are intimately linked, since the removal of certain adducts from the genome is highly dependent on their location: When such lesions are present on the transcribed strand of actively expressed genetic loci, they are better cleared from that strand when compared to the complementary DNA or other quiescent regions. This process is called transcription-coupled DNA repair, and it modulates the mutagenic spectrum of many DNA-damaging agents. Furthermore, based upon evidence from systems in which it is absent, this process has a profound effect on ameliorating the adverse consequences of exposure to many environmentally relevant genotoxins. The precise cellular pathway that mediates the preferential clearance of DNA damage from active genetic loci has not yet been established, but it appears to be effected by a repertoire of proteins that are also involved in other DNA repair pathways and transcription as well as some factors that might be unique to it. Because a cellular process as indispensable as gene expression can be thwarted by the presence of DNA damage, an understanding of the mechanism underlying transcription-coupled DNA repair is relevant to the continued discernment of how environmental genotoxins endanger human health.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalEnvironmental Health Perspectives
Volume105
Issue numberSUPPL. 1
StatePublished - Feb 1997

Fingerprint

Transcription
DNA Repair
DNA Damage
Genetic Loci
Mutagens
DNA
damage
Genome
Poisons
Health
DNA-Directed RNA Polymerases
repair
Repair
Cell Death
Nucleotides
Complementary DNA
Genes
RNA
Gene Expression
Mutation

Keywords

  • Base excision repair
  • DNA damage
  • DNA repair
  • Mismatch repair
  • Nucleotide excision repair
  • Transcription

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Transcription and DNA damage : A link to a kink. / Scicchitano, David A.; Mellon, Isabel.

In: Environmental Health Perspectives, Vol. 105, No. SUPPL. 1, 02.1997, p. 145-153.

Research output: Contribution to journalArticle

Scicchitano, David A. ; Mellon, Isabel. / Transcription and DNA damage : A link to a kink. In: Environmental Health Perspectives. 1997 ; Vol. 105, No. SUPPL. 1. pp. 145-153.
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