Journal Article

Genotoxicity of alcohol is linked to DNA replication-associated damage and homologous recombination repair

Natalia Kotova, Daniel Vare, Niklas Schultz, Dobrosława Gradecka Meesters, Maciej Stępnik, Jan Grawé, Thomas Helleday and Dag Jenssen

in Carcinogenesis

Volume 34, issue 2, pages 325-330
Published in print February 2013 | ISSN: 0143-3334
Published online November 2012 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgs340
Genotoxicity of alcohol is linked to DNA replication-associated damage and homologous recombination repair

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Although alcohol consumption is related to increased cancer risk, its molecular mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol. Here, we observe that AA effectively blocks DNA replication elongation in mammalian cells, resulting in DNA double-strand breaks associated with replication. AA-induced DNA damage sites colocalize with the homologous recombination (HR) repair protein RAD51. HR measured in the hypoxhantineguaninefosforibosyltransferase (HPRT) gene is effectively induced by AA and recombination defective mammalian cells are hypersensitive to AA, clearly demonstrating that HR is essential in the repair of AA-induced DNA damage. Altogether, our data indicate that alcohol genotoxicity related to AA produces replication lesions on DNA triggering HR repair.

Journal Article.  5115 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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