摘要
DNA损伤修复在基因突变、肿瘤发生及细胞死亡等过程中起重要作用，烷化类损伤主要由O6-甲基鸟嘌呤-DNA-甲基转移酶（O6-methylguanine-DNA methyltransferase，MGMT）修复。细胞内MGMT活性高低是肿瘤对替莫唑胺（temozolomide，TMZ）等烷化剂类化疗药产生耐药性的原因之一，其启动子甲基化与肿瘤患病风险及预后相关。研究MGMT基因表达调控对DNA损伤修复理论研究及克服肿瘤耐药均有重要意义。MGMT的表达调控机制主要包括启动子甲基化及组蛋白乙酰化、转录水平调控、转录后水平调控。
DNA damage and repair play an important role in gene mutations , tumorigenesis and cell death.DNA damage caused by alkylating agents is mainly repaired by O 6-methylguanine-DNA methyltransferase gene （MGMT） .The expression of MGMT in the cells is one of the main fac -tors responsible for the resistance of alkylating agents like temozolomide （TMZ） in tumors, and the correlation of MGMT promoter methylation with cancer risk and prognosis is also identi -fied.Understanding the mechanism of MGMT regulation can help to explore the DNA damage and re -pair and overcome the drug resistance of tumor.MGMT regulatory mechanism mainly consists of pro-moter methylation and histone acetylation , transcriptional and post-transcriptional regulation.
出处
《医学分子生物学杂志》
CAS
2014年第5期278-282,共5页
Journal of Medical Molecular Biology
基金
国家自然科学基金（No.81260501）,云南省应用基础研究计划重大项目（No.2013FC006）
