An investigation of DNA repair processes during DNA replication using the archaeon, Sulfolobus, as a model organism.

DNA突变是导致包括癌症在内的许多医学疾病的原因。这项研究的目的是进一步了解细胞如何在DNA复制过程中预防和修复DNA损伤，DNA复制是在细胞分裂之前复制的过程。人类和动物细胞中所涉及的机制的复杂性会使直接的实验观察复杂化，因此我们经常使用“简单”的模式生物来进一步了解这些过程。在这项研究中，我打算使用在高达80 ℃的恶劣环境条件下茁壮成长的单细胞模式生物来研究DNA修复的新方面。这种被称为硫化叶菌的生物属于一个古老的微生物超家族，称为古生菌，在遗传上与细菌不同。事实上，古细菌的DNA复制和修复机制与动物细胞中发现的机制更密切相关，而不是细菌中存在的机制。硫化叶菌的培养也很容易，而且成本低廉，从这些生物体中分离出的热稳定蛋白质的稳定性有利于实验研究。因此，硫化叶菌是研究复制相关DNA修复基本过程的理想生物。

Mutations in DNA are responsible for a number of medical diseases including cancers. The aim of this study is further our understanding of how cells prevent and repair DNA damage during DNA replication, the process when DNA is copied prior to cell division. The intricacy of the mechanisms involved in human and animal cells can complicate direct experimental observation, and for this reason we often use ‘simple‘ model organisms to gain further insight into these processes. In this study, I intend to examine new aspects of DNA repair using a single-celled model organism that thrives in harsh environmental conditions at temperatures of up to 80 C. This organism, called Sulfolobus, belongs to an ancient superfamily of microorganisms called archaea that are genetically distinct from bacteria. In fact, the archaeal apparatus for DNA replication and repair is more closely related to the machineries found in animal cells rather than those present in bacteria. Sulfolobus is also easy and inexpensive to cultivate, and the robustness of the heat-stable proteins isolated from these organisms facilitates experimental investigation. Therefore, Sulfolobus is an ideal organism in which to study the basic processes of replication-associated DNA repair.