Control of Genome Structure

这项拟议的研究的目的是描述粗糙脉孢菌的一种新的遗传过程，缩写为RIPING(早熟诱导的重排)。我们的初步工作表明，Riping负责高频地重新排列某些复制的DNA序列。这一过程通常还会导致受影响序列的甲基化，从头开始。我们将：(1)检验序列复制触发裂解的假设；(2)确定诱导改变的性质；(3)探索为什么某些序列表现出对该过程的抗性；(4)尝试分离RIPING缺陷突变体；(5)研究RIPING是否与一类自发突变有关。对这一过程的描述可能会阐明未知的遗传机制，同时应该为科学家对基因组进行修改提供实际使用的信息。RIPING几乎肯定是粗粒新月形藻转化DNA不稳定的原因，似乎有可能是类似RIPING的过程导致了在其他系统中观察到的DNA重排，例如在转基因小鼠中。很可能，对裂解的理解也会让我们深入了解基因组为什么是这样组织的。

The purpose of the proposed research is to characterize a novel genetic process in Neurospora crassa referred to by the acronym as "RIPing" (rearrangement induced premeiotically). Our preliminary work suggests that RIPing is responsible for rearranging certain duplicated DNA sequences at high frequency. The process also typically leads to methylation of the affected sequences, de novo. We will: (1) test the hypothesis that RIPing is triggered by sequence duplications; (2) determine the nature of the induced alterations; (3) explore why some sequences appear resistant to the process; (4) attempt to isolate mutants defective in RIPing: and (5) investigate whether RIPing is responsible for a class of spontaneous mutations. Characterization of this process may illuminate unrecognized genetic mechanisms, and at the same time should provide information of practical use to scientists making modifications to the genome. RIPing is almost certainly responsible for instability of transforming DNA in N. crassa, and it seems possible that a process analogous to RIPing is responsible for DNA rearrangements observed in other systems, such as in transgenic mice. It is likely that an understanding of RIPing will also give us insights into why the genome is organized the way it is.