GENOMIC STABILITY AND RECOMBINATIONAL INTERACTIONS

许多类型的病变的修复都需要切除， 可能是遗传多样性的来源。 DNA序列差异（同源性） 由于限制， 生物化学反应中固有的。 遗传因素，如 DNA错配修复也会影响 同源DNA 我们正在研究的要求和后果， 不同DNA之间的重组，以深入了解 重组，染色体重排的机制，并可能 致癌作用的启动机制。 我们先前已经 表明质粒DNA中的重组修复发生较少， 如果可用作修复模板的染色体DNA是有效的， 而不是同源的。 DNA错配修复能力 似乎对频率或产品几乎没有影响（检查 在分子水平上）这些重组事件。 基于这些 结果，我们建议更新版本的重组修复模型。 我们正在将这种分析扩展到其他DNA修复功能的缺陷。 为了进一步阐明错配修复对重组的影响， 分歧的DNA，我们已经研究了模型异源双链质粒， 提出的结构作为分歧之间重组的中间体 DNA 我们以前证明，一个密切相关的混合物， 异源双链体质粒以几乎相同的速率在转化中存活， 甲基指导的错配修复（MMR）-熟练的或缺陷的E.杆菌 我们 正在开发生产异源双链模型亚组分的方法， 研究特定构型对易感性的影响 MMR攻击;确切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 扩展到S.啤酒。

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.