DNA damage induced by alkylating agents and repair pathways.
DNA damage induced by alkylating agents and repair pathways.
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DOI：
10.4061/2010/543531
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发表时间：
2010-11-21
影响因子：
2.3
通讯作者：
Ohnishi T
中科院分区：
文献类型：
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作者：
Kondo N;Takahashi A;Ono K;Ohnishi T
烷化剂的细胞毒性作用被细胞DNA修复过程强烈减弱，需要清楚地了解修复机制。简单的甲基化试剂在N-和O-原子上形成加合物。N-甲基化通过碱基切除修复、AlkB同源物或核苷酸切除修复（NER）去除。O 6-甲基鸟嘌呤（MeG）可通过O 6-甲基鸟嘌呤-DNA甲基转移酶修复，O 6-MeG：T错配可通过错配修复系统（MMR）识别。MMR不能修复O 6 MeG/T错配，这最终导致双链断裂。双功能烷化剂形成更复杂且具有高度细胞毒性的链间交联（ICL）。ICL由NER因子的复合体修复（例如，核酸内切酶着色性干皮病互补组F-切除修复交叉互补啮齿动物修复缺陷互补组1）、范可尼贫血修复和同源重组。因此，详细了解细胞如何科普烷化剂引起的DNA损伤在临床医学中可能是有用的。
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). O 6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O 6-methylguanine-DNA methyltransferase, and O 6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O 6MeG/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.