GENOME STABILITY IN RAD MUTANTS

同源重组是对DNA的一种重要生物学反应 辐射和化学物质造成的损害。然而，重组必须是 控制是因为有害的基因组重排导致 重复序列之间的重组。在几个方面的观察 真核系统已经建立了序列之间的重组 长度在250个碱基对以下是严格控制的。这对于 维持基因组的稳定性，因为大多数重复 序列很短。在这个实验室里，几种辐射敏感度 (RAD)基因已被证明控制短片段之间的重组 酿酒酵母中的序列，并且这种对照是不同的 来自较长序列之间重组的控制。越远 对这种选择性控制的调查是拟议的目标 研究计划。新的缺失和易位分析将是 用来确定额外的RAD基因在对照中的作用 短重复序列重组(SRR)。这些基因在双重基因中的作用 链断裂(DSB)处理、异源双链形成和连接 将用一种新的DSB诱导来分析SRR过程中的分子形成 基因置换试验。这些基因和物理研究将结合在一起 提供独特的洞察力，了解基因组完整性是如何在 DNA损伤的后遗症。

Homologous recombination is an important biological response to DNA damage by radiation and chemicals. However, recombination must be controlled because deleterious genome rearrangements results from recombination between repeated sequences. Observations in several eukaryotic systems have established the recombination between sequences under 250 bp in length is tightly controlled. This is essential for the maintenance of genome stability because the majority of repeated sequences are short. In this laboratory, several radiation sensitivity (RAD) genes have been shown to control recombination between short sequences in the yeast S. cerevisiae, and that this control is distinct from the control of recombination between longer sequences. The further investigation of this selective control is the goal of the proposed research program. Novel deletion and translocation assays will be employed to determine the role of additional RAD genes in the control of short-repeat recombination (SRR). The role of these genes in double- strand break (DSB) processing, heteroduplex formation, and joint molecular formation during SRR will be analyzed with a novel DSB induced gene replacement assay. Together these genetic and physical studies will provide unique insight into how genomic integrity is maintained in the wake of DNA damage.