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Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts


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

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2002
Deposited On:20 Mar 2009 13:19
Last Modified:05 Apr 2016 13:03
Publisher:American Association for Cancer Research
ISSN:0008-5472
Funders:Swiss National Science Foundation, Krebsliga
Official URL:http://cancerres.aacrjournals.org/cgi/content/full/62/15/4229
PubMed ID:12154024
Permanent URL: http://doi.org/10.5167/uzh-14526

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