Lecture 24 Chapter 9 Mutations and Mutation Repair

Lecture 24 Chapter 9 Mutations and Mutation Repair 9. 1 DNA Damage and Mutations 9. 2 Point Mutations 9. 3 Insertions and Deletions 9. 4 Large-Scale DNA changes 9. 5 Consequences of DNA Mutations 9. 6 Mutation Repair 9. 7 Experiments 1 / 52 第 9章 突变与 突变修复 9. 1 DNA损伤与突变 9. 2 9. 3 9. 4 9. 5 点突变 插入和缺失 大规模DNA变化 DNA突变的后果 9. 6 突变修复 9. 7 实验研究

Review of Lecture 23 / 第 23讲复习 A 1 → Induced Mutation 诱发突变 A 2 → Insertions and Deletions 插入和缺失 A 3 → Single-strand break 单链断裂 2 / 52

A 1 → Induced Mutation 诱发突变 Induced mutations: Mutations caused by factors not normally present in the cell. 诱发突变：由通常不 是细胞的正常成分引 起的突变。 1. Base Analogues / 碱基类似物 2. Alkylating Agents / 烷化剂 3. Nitrous Acid / 亚硝酸 4. Ultraviolet Radiation / 紫外辐射 3 / 52

A 2 → Insertions and Deletions 插入和缺失 Insertion: The addition of base pairs into a DNA strand. 插入：DNA链中增加碱基 对的过程。 Deletion: The removal of base pairs from a DNA strand. 缺失：从DNA链中去除碱 基对的过程。 9. 3. 1 Strand Slippage / 链滑动 9. 3. 2 Transposons / 转座子 9. 3. 3 Intercalating Agents / 嵌入剂 4 / 52

A 3 → Single-strand break / 单链断裂 Peroxides, Fe 2+, Cu 2+ Ionizing radiation Free radicals 过氧化物、Fe 2+、Cu 2+ 电离辐射、自由基 5 / 52

Questions for Lecture 24 Q 1 → What consequences do point mutations have? 点突变会有什么后果？ Q 2 → What consequences do insertions and deletions have? 插入和缺失会有什么后果？ Q 3 → What consequences do translocations have? 易位会有什么后果？ Q 4 → Why are some DNA sites more likely to have mutation? 为什么有些DNA位点更容易发生突变？ Q 5 → How can damage on DNA be repaired? DNA损伤如何被修复呢？ 6 / 52

Vocabulary of lecture 24 silent mutation missense mutation nonsense mutation reading frameshift mutation 7 / 52 沉默突变 错义突变 无义突变 读码框 移码突变 (1/2)

Vocabulary of lecture 24 photolyase direct reversal mismatch repair nucleotide excision repair base excision repair non-homologous end joining xeroderma pigmentation Ames test 8 / 52 (2/2) 光解酶 直接回复 MMR：错配修复 NER：核苷酸切除修复 BER：碱基切除修复 NHEJ：非同源末端连接 XP：着色性干皮病 埃姆斯测验法

9. 5 Consequences of DNA Mutations DNA突变的后果 11. 5. 1 Consequences of Point Mutations 点突变的后果 11. 5. 2 Consequences of Insertions and Deletions 插入和缺失的后果 11. 5. 3 Consequences of Translocations 易位的后果 9 / 52

Q 1 → What consequences do point mutations have? 点突变会有什么后果？ 10 / 52

A 1 → 9. 5. 1 Consequences of Point Mutations / 点突变的后果 1. Silent mutation 沉默突变 2. Missense mutation 错义突变 3. Nonsense mutation 无义突变 11 / 52

1. Silent mutation / 沉默突变 Silent mutation: A point mutation that changes a base in a codon, but does not change the amino acid coded for by the codon. 12 / 52 沉默突变：在密码子 中改变了一个碱基但 没有改变密码子所编 码的氨基酸的点突变。

2. Missense mutation / 错义突变 Missense mutation: A point mutation that causes a change in one amino acid of a protein. 13 / 52 错义突变：引起蛋白质中 一个氨基酸变化的点突变。

Leaky mutation / 渗漏突变 Leaky mutation: A missense point mutation that has an affect on protein function. Normal red blood cells 14 / 52 Sickle-shaped red blood cells 渗漏突变：对蛋白质功能 有影响的一种错义点突变。

3. Nonsense mutation / 无义突变 Nonsense mutation: A point mutation that introduces a stop codon before the normal stop codon of the gene. 15 / 52 无义突变：在基因的正常 终止密码子之前产生一个 终止密码子的点突变。

Q 2 → 9. 5. 2 What consequences do insertions and deletions have? 插入和缺失会有什么后果？ 16 / 52

A 2 → Frameshift mutation / 移码突变 Frameshift mutation: A mutation that causes a shifting of the reading frame of an m. RNA. It is generally caused by insertions and deletions. 移码突变：一种引起 m. RNA读码框位置发生 变化的突变，通常由插 入和缺失引起。 Reading frame: The organization of bases in a coding region into groups of three, marked at the beginning and end by start and stop codons. 读码框：编码区中碱基以 三个一组形成的结构，以 起始密码子和终止密码子 为开始和结束的标志。 17 / 52

Frameshift mutation / 移码突变 18 / 52

“The cat ate its rat. ” hpcsc. appstate. edu/index. php? module=pagemaste. . . 19 / 52 “Txh eca tat eit sra t. ” www. deviousintentions. modblog. com 以任何不是三的倍数的数目插入或缺 失核苷酸都会产生移码突变。

Q 3 → What consequences do translocations have? 易位会有什么后果？ 20 / 52

9. 5. 3 Consequences of Translocations 易位的后果 Chronic myelogenous leukemia 慢性骨髓性白血病 Burkitt’s lymphoma 非洲淋巴瘤 21 / 52

Chronic myelogenous leukemia 慢性骨髓性白血病 biomed. brown. edu/Courses/ BI 279/Lec 12 -D. htm spsingh. net/ 22 / 52

A 3 → Translocation may result in the formation of fusion gene / 易位会导致产生融合基因 Fusion gene: A gene that is formed by fusing together two or more different genes. 23 / 52 融合基因：通过融合两个 或多个不同基因产生的基 因

Burkitt’s lymphoma / 非洲淋巴瘤 www. pathguy. com/lectures/spleen. htm What can be the reason for such vigorous growth? 25 / 52 www. gfmer. ch/. . . /Maroua_case _presentation. htm

What causes Burkitt’s lymphoma? c-myc 26 / 52

Function of gene c-myc Chromosome Gene c-Myc 2 1 Cell divides 3 Gene bci-2 4 Cell dies Apoptosis begins 27 / 52 www. geocities. com/Omegaman_UK/apoptosi. html

Q 4 → Why are some DNA sites more likely to have mutation? 为什么有些DNA位点更容易发生突变？ 前方 500米 事故 多发 地段 28 / 52

A 4 → 9. 5. 4 Mutation Hot Spots / 突变热点 Mutation hot spots: Specific DNA sites that are more likely to occur mutation than other sites. 突变热点：比其它位点更 容易发生突变的DNA位点. A mutation hot spot 29 / 52

Mutation Hot Spots / 突变热点 30 / 52

9. 6 Mutation Repair / 突变修复 31 / 52

Mutation Repair / 突变修复 32 / 52

Q 5 → How can damage on DNA be repaired? DNA损伤如何被修复呢？ 33 / 52

A 5 -1 → 9. 6. 1 Direct Reversal / 直接回复 UV light Photolyase Visible light . . . TCATTGCC AGTAACGG 34 / 52 光复活主要是原核生物中的一种修复方式。 （《遗传学》教材第 451页）

MMR: Mismatch Repair (1/2) 36 / 52

MMR: Mismatch Repair (2/2) 37 / 52

A 5 -3 → 9. 6. 3 Nucleotide Excision Repair 核苷酸切除修复 Nucleotide excision repair: A kind of excision repair usually used to fix nucleotides that have undergone large or unusual modifications. 38 / 52 核苷酸切除修复：一种 切除修复方法，通常用 来修复经受了大的或不 同寻常修饰的核苷酸。

NER: Nucleotide Excision Repair (1/2) 39 / 52

NER: Nucleotide Excision Repair (2/2) 40 / 52

MMR vs. NER MMR Mismatch 主要在复制过程 41 / 52 NER Damaged bases 在整个细胞周期

Now showing Overview of Eukaryotic Gene Expression 42 / 52 File: biophoto 7 Genetics: A Conceptual Approach Overview of eukaryotic gene expression (15’)

Essentials of Lecture 24 / 第 24讲要点 A 1 → Consequences of Point Mutations 点突变的后果 A 2 → Frameshift mutation / 移码突变 A 3 → Translocation may result in the formation of fusion gene 易位会导致产生融合基因 A 4 → Mutation Hot Spots / 突变热点 A 5 -1 → Direct Reversal / 直接回复 A 5 -2 → Mismatch Repair / 错配修复 A 5 -3 → Nucleotide Excision Repair 核苷酸切除修复 43 / 52

A 1 → 9. 5. 1 Consequences of Point Mutations / 点突变的后果 1. Silent mutation 沉默突变 2. Missense mutation 错义突变 3. Nonsense mutation 无义突变 44 / 52

A 2 → Frameshift mutation / 移码突变 Frameshift mutation: A mutation that causes a shifting of the reading frame of an m. RNA. It is generally caused by insertions and deletions. 移码突变：一种引起 m. RNA读码框位置发生 变化的突变，通常由插 入和缺失引起。 Reading frame: The organization of bases in a coding region into groups of three, marked at the beginning and end by start and stop codons. 读码框：编码区中碱基以 三个一组形成的结构，以 起始密码子和终止密码子 为开始和结束的标志。 45 / 52

A 3 → Translocation may result in the formation of fusion gene / 易位会导致产生融合基因 Fusion gene: A gene that is formed by fusing together two or more different genes. 46 / 52 融合基因：通过融合两个 或多个不同基因产生的基 因

A 4 → 9. 5. 4 Mutation Hot Spots / 突变热点 Mutation hot spots: Specific DNA sites that are more likely to occur mutation than other sites. 突变热点：比其它位点更 容易发生突变的DNA位点. A mutation hot spot 47 / 52

A 5 -1 → 9. 6. 1 Direct Reversal / 直接回复 UV light Photolyase Visible light . . . TCATTGCC AGTAACGG 48 / 52 光复活主要是原核生物中的一种修复方式。 （《遗传学》教材第 451页）

A 5 -3 → 9. 6. 3 Nucleotide Excision Repair 核苷酸切除修复 Nucleotide excision repair: A kind of excision repair usually used to fix nucleotides that have undergone large or unusual modifications. 50 / 52 核苷酸切除修复：一种 切除修复方法，通常用 来修复经受了大的或不 同寻常修饰的核苷酸。

Lecture 25 Chapter 9 Mutations and Mutation Repair 9. 1 DNA Damage and Mutations 9. 2 Point Mutations 9. 3 Insertions and Deletions 9. 4 Large-Scale DNA changes 9. 5 Consequences of DNA Mutations 9. 6 Mutation Repair 9. 7 Experiments 51 / 52 第 9章 突变与 突变修复 9. 1 DNA损伤与突变 9. 2 9. 3 9. 4 9. 5 点突变 插入和缺失 大规模DNA变化 DNA突变的后果 9. 6 突变修复 9. 7 实验研究 Teamwork 4

Questions for Lecture 25 Q 5 → How can damage on DNA be repaired? (continued) DNA损伤如何被修复呢？（续） Q 6 → What is Ames test? 什么是埃姆斯测验法？ 52 / 52