DNA Damage Induced by Alkylating Agents and Repair Pathways
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 N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleot...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.4061/2010/543531 |
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| author | Natsuko Kondo Akihisa Takahashi Koji Ono Takeo Ohnishi |
| author_facet | Natsuko Kondo Akihisa Takahashi Koji Ono Takeo Ohnishi |
| author_sort | Natsuko Kondo |
| collection | DOAJ |
| description | 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 N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/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. |
| format | Article |
| id | doaj-art-ec30f60686884dcda62e298e304eeae8 |
| institution | Kabale University |
| issn | 2090-021X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-ec30f60686884dcda62e298e304eeae82025-02-03T01:10:00ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/543531543531DNA Damage Induced by Alkylating Agents and Repair PathwaysNatsuko Kondo0Akihisa Takahashi1Koji Ono2Takeo Ohnishi3Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494, JapanDepartment of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanParticle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494, JapanDepartment of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanThe 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 N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/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.http://dx.doi.org/10.4061/2010/543531 |
| spellingShingle | Natsuko Kondo Akihisa Takahashi Koji Ono Takeo Ohnishi DNA Damage Induced by Alkylating Agents and Repair Pathways Journal of Nucleic Acids |
| title | DNA Damage Induced by Alkylating Agents and Repair Pathways |
| title_full | DNA Damage Induced by Alkylating Agents and Repair Pathways |
| title_fullStr | DNA Damage Induced by Alkylating Agents and Repair Pathways |
| title_full_unstemmed | DNA Damage Induced by Alkylating Agents and Repair Pathways |
| title_short | DNA Damage Induced by Alkylating Agents and Repair Pathways |
| title_sort | dna damage induced by alkylating agents and repair pathways |
| url | http://dx.doi.org/10.4061/2010/543531 |
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