Control of Genome Structure

提出的研究的目的是表征一个新的遗传过程在粗神经孢子虫被简称为“RIPing”（重排诱导早熟）。我们的初步工作表明，RIPing负责以高频率重新排列某些重复的DNA序列。该过程通常还会导致受影响序列的甲基化，即从头开始。我们将：(1)检验ripping由序列重复触发的假设；（二）确定引起变更的性质；(3)探究为什么某些序列对该过程产生抗性；(4)尝试分离RIPing中有缺陷的突变体；(5)研究RIPing是否导致了一类自发突变。这一过程的特征可以阐明尚未认识的遗传机制，同时应该为科学家修改基因组提供实际使用的信息。几乎可以肯定的是，RIPing是导致草棘草DNA转化不稳定的原因，而且在其他系统（如转基因小鼠）中观察到的DNA重排似乎也可能与RIPing类似。对RIPing的理解很可能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.