第4章 节 DNA复制、突变和损伤修复 药学分子生物学课件.pptVIP

2018-5-23 China Parmaceutical University 5’ 5’ 3’ 3’ 第四章 DNA的复制、突变、 损伤和修复 第一节 DNA的复制 第二节 基因突变 第三节 DNA的修复系统 2018-5-23 China Parmaceutical University Nature 455, 770-774 (9 October 2008) | doi:10.1038/nature07312 Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing Eleni P. Mimitou1 Lorraine S. Symington1 Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA DNA ends exposed after introduction of double-strand breaks (DSBs) undergo 5–3 nucleolytic degradation to generate single-stranded DNA, the substrate for binding by the Rad51 protein to initiate homologous recombination. This process is poorly understood in eukaryotes, but several factors have been implicated, including the Mre11 complex (Mre11–Rad50–Xrs2/NBS1), Sae2/CtIP/Ctp1 and Exo1. Here we demonstrate that yeast Exo1 nuclease and Sgs1 helicase function in alternative pathways for DSB processing. Novel, partially resected intermediates accumulate in a double mutant lacking Exo1 and Sgs1, which are poor substrates for homologous recombination. The early processing step that generates partly resected intermediates is dependent on Sae2. When Sae2 is absent, in addition to Exo1 and Sgs1, unprocessed DSBs accumulate and homology-dependent repair fails. These results suggest a two-step mechanism for DSB processing during homologous recombination. First, the Mre11 complex and Sae2 remove a small oligonucleotide(s) from the DNA ends to form an early intermediate. Second, Exo1 and/or Sgs1 rapidly process this intermediate to generate extensive tracts of single-stranded DNA that serve as substrate for Rad51. 2018-5-23 China Parmaceutical University 第一节 DNA的复制 一、DNA复制的一般特征 二、DNA复制中的酶学 三、原核生物的DNA复制 四、真核生物的DNA复制 2018-5-23 China Parmaceutical University 需要清楚的几个概念 复制子(replicon) 一个复制子是一个复制单位,包括复制所需的控制元件、起始点和终点; 复制子可以是线状也可以是环状; 细菌和病毒一个DNA分子就是一个复制子; 真核生物含有多个复制子,两个起始点之间的DNA片段就是一个复制子; 复制叉(replication folk) 复制时形成的Y行结构 2018-5-23 China Parmac