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因素（如阳光和电离辐射）引起的。不修复这些试剂造成的 DNA 损伤的后果是单个细胞 DNA 序列变化的积累，这些变化可以重新编程细胞，使其在不应该生长的情况下生长。这种不受控制的细胞生长是所有癌症的基础。因此，了解细胞如何响应 DNA 损伤以及如何修复此类损伤非常重要。过去使用单细胞（因此相对简单）酵母模型生物体的工作已经确定了许多 DNA 损伤反应途径，并导致人们了解这些途径如何修复 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法与人类细胞非常相似。很明显，多种相互依赖的 DNA 修复和信号传导途径可以防止突变发生，从而帮助我们避免癌症。在这个项目中，我建议研究在正常的 DNA 复制被复制块阻止后，DNA 是如何复制的。准确的 DNA 复制与 DNA 修复对于防止突变同样重要。 DNA 损伤通常会阻碍复制，这会导致一条明确的途径（即同源重组）被招募来重新启动复制。我建议确定当出现问题后通过同源重组重新开始复制​​时，哪些酶实际上复制了 DNA。