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Molecular Crosstalks at Carcinogen-DNA Adducts

  • Hanspeter Naegeli
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

To avoid damage-induced mutagenesis and minimize cytotoxicity, carcinogen-DNA adducts should be immediately channeled into appropriate repair pathways. Problems may arise, however, when a damaged sequence serves as a substrate not only for DNA repair but, simultaneously, for other nuclear functions such as transcription, replication or homologous recombination. These different processes may interfere with each other by competing for the same DNA substrate. For example, it is well established that many base lesions constitute effective blocks to transcription1 and replication.2 Analysis of UV-induced mutations in SUP4-o (a yeast transfer RNA gene transcribed by RNA polymerase III) demonstrated a strong strand bias with approximately 90% of the nucleotide sequence changes in the transcribed template strand.3 This observation indicates that excision repair in transfer RNA genes is inhibited by concurrent transcription. Exactly the opposite is observed in genes transcribed by eukaryotic RNA polymerase II, where excision repair of the transcribed template strand is stimulated by transcription.4 Thus, RNA (and DNA) polymerases are important modulators of the biological consequences of DNA damage. The role of transcription and replication in the cellular response to genotoxic insults will be reviewed in chapters 9 and 10.

Keywords

Excision Repair High Mobility Group Molecular Crosstalk Intrastrand Crosslinks Platinum Adduct 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© R.G. Landes Company 1997

Authors and Affiliations

  • Hanspeter Naegeli
    • 1
  1. 1.Institute of Pharmacology and ToxicologyUniversity of Zürich-TierspitalZürichSwitzerland

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