Topoisomerase II beta in the cellular response to DNA damage

我们的DNA有大约30亿个碱基对，编码了一个细胞在其生命周期内所有结构和功能的“蓝图”。保持DNA的完整性和稳定性对细胞和整个生物体的生存至关重要。随着每一次细胞分裂，这种DNA必须被忠实地复制并平均分配到子细胞中。它还必须准备好对任何DNA破坏事件做出反应。如果做不到这一点，可能会导致DNA突变的积累，细胞衰老或细胞死亡。令人惊讶的是，活着的有机体中的每个细胞每天都要忍受数以万计的DNA侮辱。它们自发地产生于内源(来自体内)和外源(来自体外)。矛盾的是，氧虽然对生命是绝对必要的，但作为细胞新陈代谢的副产品，它会转化为活性氧物种；这些会以多种方式改变DNA，有可能导致突变或DNA片段断裂。在地壳中发现的自然辐射，以及来自太空、航空旅行和医疗X光的暴露，都可能导致我们的DNA断裂。值得庆幸的是，已知有200多个哺乳动物基因参与了DNA损伤的检测和修复。也许矛盾的是，其他对细胞功能至关重要的蛋白质可以对DNA损伤做出反应，并被困在DNA上。这是一种潜在的危险，因为这些蛋白质可能会增加损害负担，或者减缓受损部位的修复。这些蛋白质行为的特征是一个需要深入研究的领域。这项应用通过研究拓扑异构酶IIβ(TOP2β)的这种行为，为该领域做出了贡献。

Our DNA, with ~3 billion base pairs, encodes the ‘blueprint’ for all the structures and functions of a cell over its lifespan. Maintaining the integrity and stability of this DNA is of paramount importance to survival of the cell and the entire organism. With each cell division, this DNA must be faithfully copied and equally distributed into daughter cells. It must also be prepared to react to any DNA damaging events. Failure to do so can lead to the accumulation of mutations in our DNA, cell aging or cell death. Astoundingly, each cell in a living organism endures tens of thousands of DNA insults every day. These arise spontaneously from both endogenous (from within the body) and exogenous (from outside the body) sources. Paradoxically, oxygen, although absolutely essential for life, is converted to reactive oxygen species as by-products of cell metabolism; these can alter DNA in numerous ways, potential leading to mutations or broken DNA fragments. Naturally occurring radiation found in the earth’s crust and exposure from space, airline travel and medical x-rays can lead to breaks in our DNA. Thankfully, over 200 mammalian genes are known to be involved in the detection and repair of DNA damage. Perhaps paradoxically, other proteins critical for cell function can react to DNA damage and become trapped on the DNA. This is a potential hazard, as these proteins could add to the damage burden, or slow the repair of damage sites. Characterization of these protein behaviours is an area of intense investigation. This application contributes to the field by investigating this behaviour for one enzyme, topoisomerase IIβ (TOP2β).