2013DNA复制修复重组资料分析.ppt

单个核苷酸的改变导 致镰状细胞贫血病 癌症发病率是随着年龄 增长的函数而急剧增加 Deletion or Insertion （缺失或插入） The elimination or addition of one or more nucleotides in a DNA region. It may cause frameshift (移码突变) producing a non-functional protein. Real examples of deletion mutations which cause diseases In CFTR gene In CFTR gene 囊性纤维跨膜电导调节因子 In FIX gene 凝血因子IX9号 In APC gene 结肠腺癌性息肉 Serious Consequences of Insertion Mutation Replication fidelity (复制的精确性) Mutation relevant Spontaneous errors in DNA replication is very rare, one error per 1010 base in E. coli, which is much less than the error that DNA polymerase III introduced. Important for preserve the genetic information from one generation to the next. This increased accuracy in vivo is largely due to the proofreading function of E. coli DNA polymerases Proofreading refers to any mechanism for correcting errors in protein or nucleic acid synthesis that involves scrutiny of individual units after they have been added to the chain. Proofreading function of E. coli DNA polymerases Experimental demonstration of the proofreading function of E. coli DNA polymerase I. [See A. Kornberg and T. A. Baker, 1992, DNA Replication, 2d ed., W. H. Freeman and Company.] DNA聚合酶含有DNA合成和校读 两个不同的位点 聚合 校读 Proofreading function of E. coli DNA polymerases When an incorrect base is incorporated during DNA synthesis, the polymerase pauses, then transfers the 3’ end of the growing chain to the exonuclease site where the mispaired base is removed. Then the 3’ end flips back into the polymerase site, where this region is copied correctly. Proofreading play a critical role in maintaining sequence fidelity during replication ? E. coli DNA polymerase I (3’ → 5’ exonuclease activity ) and DNA polymerase III (ε subunit of the core polymerase ) have proofreading activity. ? In animal cells, both of the δ and ε DNA polymerases, but not the α polymerase, have proofreading act