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Journal of Nucleic Acids
Volume 2010, Article ID 543531, 7 pages
http://dx.doi.org/10.4061/2010/543531
Review Article

DNA Damage Induced by Alkylating Agents and Repair Pathways

1Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan
2Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan
3Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan

Received 8 June 2010; Revised 26 August 2010; Accepted 12 October 2010

Academic Editor: Ashis Basu

Copyright © 2010 Natsuko Kondo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at - and -atoms. -methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). -methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by -methylguanine-DNA methyltransferase, and MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine.