MOLECULAR MECHANISMS OF GENETIC RECOMBINATION

本研究的长期目标是 了解同源重组的分子机制 以及DNA中碱基错配修复的机制， 这些过程。 这些目标通过生物化学方法实现， 研究促进重组和修复的酶， 通过研究在这些过程中改变的突变生物体来遗传。 研究的重点是重组的RecBCD途径， 大肠杆菌，粟酒酵母中的减数分裂重组， 和错配修复。Pombe. 研究的具体目标是：大肠杆菌是1）确定物理 在Chi位点的RecBCD酶的变化，和2）阐明 RecBCD酶解链DNA的机制。 研究的具体目标是在S。粟酒裂殖子是1）分析减数分裂 重组缺陷（rec）突变体，re基因及其产物， 2)使用物理分析寻找重组中间体，以及 确定其形成的rec基因要求，以及3） 确定核酸外切酶I和其他组分在 错配修复 生物多样性是生物多样性的重要组成部分， 有机体和细胞水平。 重组的异常产生 染色体重排，如缺失和易位。 染色体重排与，并可能是一个原因 出生缺陷和癌症。 了解分子机制 重组的重要性在于确定这些原因 疾病，并可能预防它们。 错配修复缺陷 与几种癌症有关 识别 错配修复的组成部分可能导致早期诊断， 预防癌症。

The long-term objection of the research proposed here is to understand the molecular mechanisms of homologous recombination and of base-mismatch repair in DNA, and the mechanisms that control these processes. These objectives are approached biochemically by studying the enzymes promoting recombination and repair, and genetically by studying mutant organisms altered in these processes. The research is focused on the RecBCD pathway of recombination in Escherichia coli, meiotic recombination in schizosaccharomyces pombe, and mismatch repair in S. Pombe. Specific aims of the research in E. coli are to 1) determine the physical change of RecBCD enzyme at Chi sites, and 2) elucidate the mechanism of DNA unwinding by RecBCD enzyme. Specific aims of the research in S. pombe are to 1) analyze meiotic recombination-deficient (rec) mutants, the re genes and their products, 2) search for recombination intermediates, using a physical assay, and determine the rec gene requirements for their formation, and 3) determine the roles of exonuclease I and additional components in mismatch repair. Recombination is important for generating diversity at both the organismal and cellular levels. Aberrancies of recombination generate chromosomal rearrangements, such as deletions and translocations. Chromosomal rearrangements are associated with, and may be a cause of, birth defects and cancers. Understanding the molecular mechanism of recombination is important in determining the causes of these diseases and possibly preventing them. Mismatch repair-deficiencies are associated with several types of cancer. Identifying the components of mismatch repair may lead to early diagnosis and prevention of cancer.