Studies Of DNA Mismatch Repair

今年，我们继续研究错配修复在调节酵母细胞全基因组突变率中的作用，酵母细胞含有主要前导链和滞后链酶，DNA聚合酶epsilon和delta的变异等位基因。这些研究是在错配修复熟练和缺陷酵母细胞中进行的，如该实验室的另一份年度报告1 Z01 ES065070-27: DNA复制保真度的结构-功能研究。它们目前包括今年发表的一项关于缺乏MMR的酵母细胞复制的研究，该研究显示了MMR缺失对细胞中已报道的基因特异性突变率的影响。此外，我们继续使用名为Muver的新技术，该技术大大提高了我们在mmr缺陷细胞和熟练细胞中测量全基因组突变率的能力。这项技术对核苷酸选择性、校对和错配修复对碱基替换和插入缺失错误的全基因组突变率的贡献提供了非常丰富的信息。它被用于目前正在进行但尚未发表的全基因组突变率研究。

This year, we continued to study the role of mismatch repair in regulating the genome-wide mutation rates of yeast cells harboring variant alleles of the major leading and lagging strand enzymes, DNA polymerases epsilon and delta. These studies are performed in mismatch repair proficient and deficient yeast cells, as reported in the other annual report from this laboratory, 1 Z01 ES065070-27: Structure-Function Studies of DNA Replication Fidelity. They currently include a study published this year on replication in yeast cells deficient in MMR showing the consequences of loss of MMR on reported gene specific mutation rates in cells. In addition, we continue to use the new technology called Muver that greatly improves our ability to measure genome-wide mutation rates in MMR-deficient and proficient cells. This technology is very informative regarding the contributions of nucleotide selectivity, proofreading and mismatch repair to genome wide mutation rates for base substitution and insertion-deletion errors. It is being used for studies of genome-wide mutation rates that are currently underway but not yet published.