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Correlation of sister chromatid exchange formation through homologous recombination with ribonucleotide reductase inhibition.
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
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2004 (English)In: Mutat Res, ISSN 0027-5107, Vol. 547, no 1-2, 101-7 p.Article in journal (Other academic) Published
Abstract [en]

We conducted the recombination and sister chromatid exchange (SCE) assays with five chemicals (hydroxyurea (HU), resveratrol, 4-hydroxy-trans-stilbene, 3-hydroxy-trans-stilbene, and mitomycin C) in Chinese hamster cell line SPD8/V79 to confirm directly that SCE is a result of homologous recombination (HR). SPD8 has a partial duplication in exon 7 of the endogenous hprt gene and can revert to wild type by homologous recombination. All chemicals were positive in both assays except for 3-hydroxy-trans-stilbene, which was negative in both. HU, resveratrol, and 4-hydroxy-trans-stilbene were scavengers of the tyrosyl free radical of the R2 subunit of mammalian ribonucleotide reductase. Tyrosyl free radical scavengers disturb normal DNA replication, causing replication fork arrest. Mitomycin C is a DNA cross-linking agent that also causes replication fork arrest. The present study suggests that replication fork arrest, which is similar to the early phases of HR, leads to a high frequency of recombination, resulting in SCEs. The findings show that SCE may be mediated by HR.

Place, publisher, year, edition, pages
2004. Vol. 547, no 1-2, 101-7 p.
Keyword [en]
Alkylating Agents/toxicity, Animals, CHO Cells, Cricetinae, Cricetulus, Crossing Over; Genetic/*drug effects, DNA Replication, Enzyme Inhibitors/toxicity, Hydroxyurea/toxicity, Mitomycin/toxicity, Protein Subunits/drug effects, Ribonucleotide Reductases/*antagonists & inhibitors/chemistry/drug effects, Sister Chromatid Exchange, Stilbenes/toxicity, Structure-Activity Relationship, Time Factors
URN: urn:nbn:se:su:diva-20346PubMedID: 15013704OAI: diva2:186872
Available from: 2007-03-10 Created: 2007-03-10 Last updated: 2011-01-12Bibliographically approved

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Lundin, CeciliaJohansson, FredrikSahlin, MargaretaSjöberg, Britt-MarieJenssen, Dag
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Department of Molecular Biology and Functional Genomics

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