Wyatt M D, Allan J M, Lau A Y, Ellenberger T E, Samson L D
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Bioessays. 1999 Aug;21(8):668-76. doi: 10.1002/(SICI)1521-1878(199908)21:8<668::AID-BIES6>3.0.CO;2-D.
The genome continuously suffers damage due to its reactivity with chemical and physical agents. Finding such damage in genomes (that can be several million to several billion nucleotide base pairs in size) is a seemingly daunting task. 3-Methyladenine DNA glycosylases can initiate the base excision repair (BER) of an extraordinarily wide range of substrate bases. The advantage of such broad substrate recognition is that these enzymes provide resistance to a wide variety of DNA damaging agents; however, under certain circumstances, the eclectic nature of these enzymes can confer some biological disadvantages. Solving the X-ray crystal structures of two 3-methyladenine DNA glycosylases, and creating cells and animals altered for this activity, contributes to our understanding of their enzyme mechanism and how such enzymes influence the biological response of organisms to several different types of DNA damage.
基因组因其与化学和物理因子的反应性而不断遭受损伤。在大小可能达数百万至数十亿个核苷酸碱基对的基因组中发现此类损伤似乎是一项艰巨的任务。3-甲基腺嘌呤DNA糖基化酶可启动范围极为广泛的底物碱基的碱基切除修复（BER）。这种广泛的底物识别优势在于这些酶对多种DNA损伤剂具有抗性；然而，在某些情况下，这些酶的兼收并蓄特性可能会带来一些生物学劣势。解析两种3-甲基腺嘌呤DNA糖基化酶的X射线晶体结构，并创建针对该活性改变的细胞和动物，有助于我们理解它们的酶作用机制以及此类酶如何影响生物体对几种不同类型DNA损伤的生物学反应。
