GENOME STABILITY IN RAD MUTANTS

RAD 突变体的基因组稳定性

基本信息

批准号：
6386884
负责人：
ADAM M BAILIS
金额：
$ 24.86万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-05-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6386884
关键词：
DNA DNA damage DNA repair Saccharomyces cerevisiae chromosome translocation fungal genetics gene deletion mutation gene mutation gene rearrangement genetic recombination mutant nucleic acid repetitive sequence polymerase chain reaction radiation dosage radiation genetics radiation sensitivity southern blotting

项目摘要

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.

同源重组是DNA的重要生物反应辐射和化学物质造成的损害。但重组必须是受到控制，因为有害的基因组重排是由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低于 250 bp 的片段受到严格控制。这对于维持基因组稳定性，因为大多数重复序列很短。在这个实验室中，几种辐射敏感性（RAD）基因已被证明可以控制短片段之间的重组酿酒酵母中的序列，并且这种控制是独特的来自较长序列之间重组的控制。进一步的对这种选择性控制的调查是拟议的目标研究计划。新的缺失和易位测定将用于确定其他 RAD 基因在对照中的作用短重复重组（SRR）。这些基因在双链断裂 (DSB) 加工、异源双链体形成和连接 SRR 期间的分子形成将通过新型 DSB 诱导进行分析基因替代测定。这些遗传和物理研究共同将提供关于如何维持基因组完整性的独特见解 DNA损伤后。