基因突变与修复 MBg-17 Mutability and Repair of DNA.ppt

A common cause of hotspots is the modified base 5-methylcytosine, which is spontaneously deaminated to thymine. 基因突变的表达类型 突变体是遗传学研究的重要物质基础。虽然突变体可以通过人工诱变和自然筛选等方法获得，但突变性状的表现可以是“条件型’’和“非条件型”的。绝大部分突变性状的表现是“非条件型”的，而且这类突变体易于保存。所谓“条件型’’突变性状是指在一定的环境条件下或某种遗传背景下，突变性状才得以表现的类型。例如与DNA复制有关的温度敏感型突变基因，在正常37℃条件下突变基因不表达，生物个体可以进行正常的DNA复制，并保存突变体材料。只有在42℃条件下，温度敏感有关基因才表达。氨酰tRNA合成酶温度敏感型突变基因，禾谷类作物的光敏感雄性不育基因均属于“条件型”突变基因。另一类“条件型”突变基因的表达需在非抑制基因(su-)存在的遗传背景下才能表达，在具有su+抑制基因的背景下，突变基因的表达被抑制，突变性状不能表现。 基因的诱发突变 根据诱发基因突变外界因素的种类，突变可分为物理诱变和化学诱变。随着生物技术的发展，基因的定点诱变技术，转座子和Ti质粒介导的插入突变，DNA片段的“洗牌 ” (shuffling)技术等已受到广泛的重视，并在分子生物学研究中形成体外分子进化(molecular evolution)的新领域。 物理诱变的诱变因素可分为电离辐射和非电离辐射两大类。 用于化学诱变的诱变剂依其作用机制可大体分为4类: 1．抑制碱基合成的诱变剂 这类诱变剂主要有抑制嘧啶合成的5-氨基尿嘧啶和抑制嘌呤合 成的6-巯基嘌呤． 2．碱基类似物 这类诱变剂主要有5-溴尿嘧啶(5-BrU，)和2-氨基嘌呤(2-AP)。 3. 修饰碱基结构的诱变剂（亚硝酸，羟胺和烷化剂）。 4. 插入诱变剂（EB等）。 The Mutability and Repair of DNA Three important sources of mutation are: ◆ Inaccuracy in DNA replication ◆ Radiation and chemical damage to the genetic material ◆ DNA insertions generated by DNA elements known as transposons The challenge for the cell is twofold 双重的: ◆ First, it must scan the genome to detect errors in synthesis and damage to the DNA. ◆ Second, it must mend the lesions and do so in a way that, if possible, restores the original DNA sequence. We shall consider how the alteration to the genetic material is detected and how it is properly repaired. Among the questions we shall address are the following: How is the DNA mended rapidly enough to prevent errors from becoming set in the genetic material as mutations? How does the cell distinguish the parental strand from the daughter strand in repairing replication errors? How does the cell restore the proper DNA sequence when, due to a break or severe lesion, the original sequence can no longer be read? How does the cell cope with lesions that block replication? The answers to these questions de