ILLEGITIMATE RECOMBINATION IN YEAST

拟议研究的长期目标是了解 重组事件涉及很少或不涉及DNA序列同源性。 这类事件已通过多种方式被发现。 例如当 哺乳动物细胞用DNA转化，转化序列 通常通过非同源重组整合到染色体中 活动 相比之下，在酵母菌中转化DNA 据报道，酿酒酵母仅通过以下方式整合到基因组中： 同源重组 最近，将转化DNA整合到 已经观察到通过非同源重组的酵母。 在这 建议，管理这种重组的规则将是 考察 特别是这种交换的遗传控制 将通过选择具有更高（或更低）水平的突变体来研究 不合理的重组。 还将确定是否 转化DNA的非法整合与形成 染色体缺失的证据。 由于非法融合 事件是基因治疗方案开发中的一个严重问题， 治疗，这些研究应该与健康相关的问题。 一 建议研究的第二个领域是重组事件的分析 由外源性限制性内切酶催化。 使用这种 用于插入诱变的技术，以及用于产生 将检查染色体畸变。

The long-term objective of the proposed research is to understand recombination events that involve little or no DNA sequence homology. Such events have been detected in a number of ways. For example, when mammalian cells are transformed with DNA, the transforming sequences usually integrate into the chromosome by a non-homologous recombination event. In contrast, transforming DNA in the yeast Saccharomyces cerevisiae has been reported to integrate into the genome only by homologous recombination. Recently, integration of transforming DNA in yeast by non-homologous recombination has been observed. In this proposal, the rules governing this type of recombination will be examined. In particular, the genetic control of this type of exchange will be investigated by selecting mutants with higher (or lower) levels of illegitimate recombination. It will also be determined whether the illegitimate integration of transforming DNA is related to the formation of chromosomal deletions in yeast. Since illegitimate integration events are a serious problem in the development of protocols for gene therapy, these studies should be relevant to health-related problems. A second area of proposed research is the analysis of recombination events catalyzed by exogenously-added restriction enzymes. The use of this technique for insertional mutagenesis, and for the creation of chromosomal aberrations will be examined.