Abstract

Purpose

To summarize succinctly the 50 years of research undertaken in my laboratory and to provide an overview of my career in science. It is certainly a privilege to have been asked by Carmel Mothersill and Penny Jeggo to contribute to this special issue of the International Journal of Radiation Biology focusing on the work of women in the radiation sciences.

Conclusion

My students, post-docs and I identified and characterized a number of the enzymes that recognize and remove radiation-damaged DNA bases, the DNA glycosylases, which are the first enzymes in the Base Excision Repair (BER) pathway. Although this pathway actually evolved to repair oxidative and other endogenous DNA damages, it is also responsible for removing the vast majority of radiation-induced DNA damages including base damages, alkali-labile lesions and single strand breaks. However, because of its high efficiency, attempted BER of clustered lesions produced by ionizing radiation, can have disastrous effects on cellular DNA. We also evaluated the potential biological consequences of many of the radiation-induced DNA lesions. In addition, with collaborators, we employed computational techniques, x-ray crystallography and single molecule approaches to answer many questions at the molecular level.

中文翻译：

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辐射引起的 DNA 损伤的后果和修复：五十年有趣的问答

摘要

目的

简明扼要地总结我在实验室进行的 50 年研究，并概述我在科学领域的职业生涯。很荣幸受到 Carmel Mothersill 和 Penny Jeggo 的邀请，为本期《国际放射生物学杂志》特刊撰稿，该杂志关注女性在放射科学领域的工作。

结论

我的学生、博士后和我鉴定并表征了许多识别和去除辐射损伤的 DNA 碱基的酶，即 DNA 糖基化酶，它们是碱基切除修复 (BER) 途径中的第一个酶。尽管该途径实际上进化为修复氧化和其他内源性 DNA 损伤，但它也负责消除绝大多数辐射诱导的 DNA 损伤，包括碱基损伤、碱不稳定损伤和单链断裂。然而，由于其高效率，电离辐射产生的簇状损伤的尝试 BER 可能对细胞 DNA 产生灾难性影响。我们还评估了许多辐射诱导的 DNA 损伤的潜在生物学后果。此外，与合作者一起，我们采用了计算技术，