Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts

Tonko Buterin, Martin T. Hess, Daniela Gunz, Nicholas Geacintov, Leon H. Mullenders, Hanspeter Naegeli

Research output: Contribution to journalArticle

Abstract

Nucleotide excision repair is part of a cellular defense system that protects genome integrity. Here, this versatile repair system was challenged with mixtures of DNA adducts that were generated to mimic the wide spectrum of bulky lesions produced by complex genotoxic insults. Probing human excision activity with substrate combinations instead of single lesions resulted in a strong bias for particular base adducts, such that the repair factors were immobilized on a small fraction of damaged DNA, whereas the simultaneous excision of other sites was suppressed. Immobilization of excision factors was also induced by nonrepairable decoy adducts, thereby revealing a mechanism of repair inhibition because of hijacking of critical subunits. Thus, the efficiency of excision repair in response to bulky carcinogen-DNA damage is dependent on an antagonistic interaction with both substrate and decoy adducts.

Original languageEnglish (US)
Pages (from-to)4229-4235
Number of pages7
JournalCancer Research
Volume62
Issue number15
StatePublished - Aug 1 2002

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DNA Repair
Carcinogens
DNA Adducts
DNA
Human Activities
Immobilization
DNA Damage
Genome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Buterin, T., Hess, M. T., Gunz, D., Geacintov, N., Mullenders, L. H., & Naegeli, H. (2002). Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts. Cancer Research, 62(15), 4229-4235.

Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts. / Buterin, Tonko; Hess, Martin T.; Gunz, Daniela; Geacintov, Nicholas; Mullenders, Leon H.; Naegeli, Hanspeter.

In: Cancer Research, Vol. 62, No. 15, 01.08.2002, p. 4229-4235.

Research output: Contribution to journalArticle

Buterin, T, Hess, MT, Gunz, D, Geacintov, N, Mullenders, LH & Naegeli, H 2002, 'Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts', Cancer Research, vol. 62, no. 15, pp. 4229-4235.
Buterin T, Hess MT, Gunz D, Geacintov N, Mullenders LH, Naegeli H. Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts. Cancer Research. 2002 Aug 1;62(15):4229-4235.
Buterin, Tonko ; Hess, Martin T. ; Gunz, Daniela ; Geacintov, Nicholas ; Mullenders, Leon H. ; Naegeli, Hanspeter. / Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts. In: Cancer Research. 2002 ; Vol. 62, No. 15. pp. 4229-4235.
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