Which DNA polymerase functions during HR-dependent fork restart?

哪种 DNA 聚合酶在 HR 依赖性分叉重启期间发挥作用？

• 批准号: G0801078/1
• 负责人: Antony Carr
• 金额: $ 32.32万
• 依托单位: University of Sussex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801078%2F1
• 关键词: DNA; polymerase; functions; during; HR

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.

DNA损伤是由内部DNA损伤剂（如氧）引起的，与正常寿命以及来自阳光和电离辐射等体内外部的药物相关。不修复这些药物引起的DNA损伤的后果是，单个细胞的DNA序列的变化积累，这些变化可以在不应生长时重新编程细胞生长。这种不受控制的细胞生长是所有癌症的基础。因此，重要的是要了解细胞如何应对DNA损伤以及如何修复这种损伤。过去使用单细胞（因此相对简单）酵母模型生物的工作鉴定了许多DNA损伤响应途径，并导致对这些功能如何修复DNA损伤的功能以及在DNA受损时如何划分细胞分裂。通过使用这些易于操纵的酵母模型系统，科学家能够定义DNA损伤响应途径使用的许多基本分子机制，并在其他细胞过程中检查这些功能。重要的是，尽管酵母菌相对简单，但它们使用非常相似的方法来处理这些问题，就像人类细胞一样。很明显，多个相互依赖性的DNA修复和信号通路可以防止发生突变，从而有助于我们避免癌症。在这个项目中，我建议研究如何通过复制块阻止正常DNA复制后复制DNA。准确的DNA复制与预防突变中的DNA修复一样重要。 DNA损伤通常会阻止复制，这会导致定义的途径，同源重组，并被招募以重新启动复制。我建议在出现问题后通过同源重组重新启动复制重新启动时实际上复制了哪种酶。