Which DNA polymerase functions during HR-dependent fork restart?

DNA损伤是由与正常生活相关的内部DNA损伤剂（如氧气）和来自我们身体外部的试剂（如阳光和电离辐射）引起的。不修复由这些试剂引起的DNA损伤的后果是单个细胞的DNA序列变化的积累，这些变化可以重新编程细胞在不应该生长的时候生长。这种不受控制的细胞生长是所有癌症的基础。因此，重要的是我们要了解细胞如何对DNA损伤做出反应，以及它们如何修复这种损伤。使用单细胞（因此相对简单）酵母模型生物的工作在过去已经确定了许多DNA损伤反应途径，并导致了解这些功能如何修复DNA损伤并防止细胞在DNA受损时分裂。通过使用这些易于操作的酵母模型系统，科学家们已经能够定义DNA损伤反应途径所使用的许多基本分子机制，并在其他细胞过程的背景下检查这些功能。重要的是，虽然酵母相对简单，但它们处理这些问题的方式与人类细胞非常相似。很明显，多个相互依赖的DNA修复和信号通路可以防止突变的发生，从而帮助我们避免癌症。在这个项目中，我建议研究如何复制后，正常的DNA复制已被复制块阻止。准确的DNA复制与DNA修复在预防突变方面同样重要。DNA损伤通常会阻断复制，这导致一个确定的途径，同源重组，被招募重新启动复制。我建议确定哪些酶实际上复制的DNA时，复制是重新启动同源重组后出现的问题。

DNA damage is caused by both internal DNA damaging agents (like oxygen) that are associated with normal life and by agents from outside our bodies such as sunlight and ionising radiation. The consequences of not repairing the DNA damage caused by these agents are the accumulation of changes in the DNA sequence of individual cells that can reprogram the cell to grow when it should not be growing. Such uncontrolled cell growth is the basis of all cancers. It is therefore important that we understand how cells respond to DNA damage and how they repair such damage. Work using single celled (and thus relatively simple) yeast model organisms has in the past identified many DNA damage response pathways and lead to an understanding of how these function to both repair DNA damage and to prevent cells dividing when their DNA is damaged. By using these easily manipulated yeast model systems, scientists have been able to define many of the fundamental molecular mechanisms used by DNA damage response pathways and to examine these functions in the context of other cellular processes. Importantly, while yeasts are relatively simple, they use very similar ways of dealing with these problems as human cells do. It has become clear that multiple inter-dependent DNA repair and signalling pathways act to prevent mutations occurring and thus help us avoid cancer. In this project I propose to study how the DNA is replicated after normal DNA replication has been prevented by replication blocks. Accurate DNA replication is as important as DNA repair in preventing mutations. DNA damage often blocks replication and this results in a defined pathway, homologous recombination, being recruited to restart replication. I propose to establish which enzymes actually replicated the DNA when replication is restarted by homologous recombination after problems have occurred.