Weinfeld M, Rasouli-Nia A, Chaudhry M A, Britten R A
Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada.
Radiat Res. 2001 Nov;156(5 Pt 2):584-9. doi: 10.1667/0033-7587(2001)156[0584:robere]2.0.co;2.
There is now increasing evidence that ionizing radiation generates complex DNA damage, i.e. two or more lesions--single-strand breaks or modified nucleosides--located within one to two helical turns on the same strand or on opposite strands. Double-strand breaks are the most readily recognizable clustered lesions, but they may constitute a relatively minor fraction of the total. It is anticipated that clustered lesions may play a significant role in cellular response to ionizing radiation since they may present a major challenge to the DNA repair machinery. The degree of lesion complexity increases with increasing LET. This has potential implications for space travel because of exposure to high-LET cosmic radiation. It is therefore critical that we begin to understand the consequences of such damaged sites, including their influence on DNA repair enzymes. This paper presents a short review of our current knowledge of the action of purified DNA repair enzymes belonging to the base excision repair pathway, including DNA glycosylases and apurinic/apyrimidinic endonucleases, on model complex lesions.
现在越来越多的证据表明，电离辐射会产生复杂的DNA损伤，即位于同一链或相反链上一到两个螺旋圈范围内的两个或更多损伤——单链断裂或修饰核苷。双链断裂是最容易识别的簇状损伤，但它们可能只占总数的相对较小部分。由于簇状损伤可能对DNA修复机制构成重大挑战，预计它们在细胞对电离辐射的反应中可能起重要作用。损伤复杂性程度随传能线密度（LET）增加而增加。由于暴露于高传能线密度的宇宙辐射，这对太空旅行具有潜在影响。因此，至关重要的是我们要开始了解此类受损位点的后果，包括它们对DNA修复酶的影响。本文简要综述了我们目前对属于碱基切除修复途径的纯化DNA修复酶，包括DNA糖基化酶和脱嘌呤/脱嘧啶内切核酸酶，对模型复杂损伤作用的认识。
