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Nucleic Acids Research, 2003, Vol. 31, No. 23 7032-7040
© 2003 Oxford University Press

Article

Repair of single-strand DNA interruptions by redundant pathways and its implication in cellular sensitivity to DNA-damaging agents

Erick L. Y. Ho and Masahiko S. Satoh*

Laboratory of DNA Repair, Health and Environment Unit, Laval University Medical Center, CHUQ, Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Ste-Foy, Quebec G1V 4G2, Canada

*To whom all correspondence should be addressed. Tel: +1 418 656 4141 ext. 47340; Fax: +1 418 654 2159; Email: masahiko.sato{at}crchul.ulaval.ca

Single-strand DNA interruptions (SSIs) are produced during the process of base excision repair (BER). Through biochemical studies, two SSI repair subpathways have been identified: a pathway mediated by DNA polymerase ß (Pol ß) and DNA ligase III (Lig III), and a pathway mediated by DNA polymerase {delta}/{epsilon} (Pol {delta}/{epsilon}) and DNA ligase I (Lig I). In addition, the existence of another pathway, mediated by Pol ß and DNA Lig I, has been suggested. Although each pathway may play a unique role in cellular DNA damage response, the functional implications of SSI repair by these three pathways are not clearly understood. To obtain a better understanding of the functional relevance of SSI repair by these pathways, we investigated the involvement of each pathway by monitoring the utilization of DNA ligases in cell-free extracts. Our results suggest that the majority of SSIs produced during the repair of alkylated DNA bases are repaired by the pathway mediated by Pol ß and either Lig I or Lig III, although some SSIs are repaired by Pol {delta}/{epsilon} and Lig I. At a cellular level, we found that Lig III over-expression increased the resistance of cells to DNA-damaging agents, while Lig I over-expression had little effect. Thus, repair pathways mediated by Lig III may have a role in the regulation of cellular sensitivity to DNA-damaging agents.


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