GENOMIC STABILITY AND RECOMBINATIONAL INTERACTIONS

许多类型的病变的修复都需要重组，而它 可能是遗传多样性的一个来源。DNA序列差异(同源) 由于受到限制，预计会阻碍重组效率 在生化反应中固有的。辅助遗传因素，如 DNA错配修复也有望影响 同源DNA。我们正在研究以下要求和后果 不同DNA之间的重组以深入了解其发病机制 重组，染色体重排的机制，以及可能的 致癌机制的研究进展。我们之前已经 证明了重组修复在质粒DNA中发生的次数较少 如果可用作修复模板的染色体DNA是有效的 同源的而不是同源的。精通DNA错配修复 似乎对频率或产物影响很小或没有影响(检查 在分子水平上)这些重组事件。基于这些 结果，我们建议进行重组修复的模型的更新版本。 我们正在将这一分析扩展到其他DNA修复功能的缺陷。 进一步阐述错配修复对基因重组的影响 发散的DNA，我们研究了类似于 被认为是分叉之间重组的中间体的结构 DNA。我们之前证明了一种密切相关的混合体 异源双链质粒在转化过程中存活的速度几乎相同 甲基定向错配修复(MMR)-熟练或缺陷的大肠杆菌。我们 正在开发生产模型异双链亚馏分的方法 研究特定构型对易感性的影响的质粒 通过MMR攻击；准确的配置是一个重要的参数 重组修复模型。这些实验目前正在进行 扩展到酿酒酵母。

Recombination is required for the repair of many types of lesions and it can be a source of genetic diversity. DNA sequence divergence (homoeology) is expected to impede recombination efficiency because of constraints inherent in the biochemical reactions. Ancillary genetic factors such as DNA-mismatch repair are also expected to affect recombination between homologous DNAs. We are examining the requirements and consequences of recombination between divergent DNAs to gain insight on mechanisms of recombination, mechanisms of chromosome rearrangements, and possibly mechanisms of initiation of carcinogenesis. We have previously demonstrated that recombinational repair in plasmid DNA occurs less efficiently if the chromosomal DNA available as the template for repair is homeologous rather than homologous. Proficiency for DNA mismatch repair appears to have little or no effect on the frequency or products (examined at the molecular level) of these recombination events. Based on these results, we suggest updated versions of models for recombinational repair. We are extending this analysis to defects in other DNA repair functions. To further elaborate the effect of mismatch repair on recombination between diverged DNAs, we have studied model heteroduplex plasmids which resemble structures proposed as intermediates in recombination between diverged DNAs. We previously demonstrated that a mixture of closely related heteroduplex plasmids survive transformation at nearly the same rate in methyl-directed mismatch repair (MMR)-proficient or deficient E. coli. We are developing methods of producing subfractions of model heteroduplex plasmids to study the effects of specific configurations on susceptibility to attack by MMR; the exact configuration is an important parameter in models of recombination repair. These experiments are currently being extended to S. cerevisiae.