Lecture 24

1. Lecture 24 第9章 突变与 突变修复 9.1 DNA损伤与突变 9.2点突变 9.3 插入和缺失 9.4 大规模DNA变化 9.5 DNA突变的后果 9.6 突变修复 9.7 实验研究 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

2. Review of Lecture 23 / 第23讲复习 A1→ Induced Mutation诱发突变 A2→ Insertions and Deletions插入和缺失 A3→ Single-strand break 单链断裂

3. A1→ Induced Mutation诱发突变 诱发突变：由通常不是细胞的正常成分引起的突变。 Induced mutations:Mutations caused by factors not normally present in the cell. 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

4. A2→ Insertions and Deletions插入和缺失 插入：DNA链中增加碱基对的过程。 Insertion:The addition of base pairs into a DNA strand. 缺失：从DNA链中去除碱基对的过程。 Deletion:The removal of base pairs from a DNA strand. 9.3.1 Strand Slippage / 链滑动 9.3.2 Transposons / 转座子 9.3.3 Intercalating Agents / 嵌入剂

5. A3→ Single-strand break / 单链断裂 Peroxides, Fe2+, Cu2+ Ionizing radiation Free radicals 过氧化物、Fe2+、Cu2+ 电离辐射、自由基

6. Questions for Lecture 24 Q1→ What consequences do point mutations have? 点突变会有什么后果？ Q2→ What consequences do insertions and deletions have? 插入和缺失会有什么后果？ Q3→ What consequences do translocations have? 易位会有什么后果？ Q4→ 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？ Q5→ How can damage on DNA be repaired? DNA损伤如何被修复呢？

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

8. Vocabulary of lecture 24 (2/2) photolyase direct reversal mismatch repair nucleotide excision repair base excision repair non-homologous end joining xeroderma pigmentation Ames test 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. 9.5 Consequences of DNA MutationsDNA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

10. Q1→ What consequences do point mutations have? 点突变会有什么后果？

11. A1→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

12. 1. Silent mutation / 沉默突变 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。 Silent mutation: A point mutation that changes a base in a codon, but does not change the amino acid coded for by the codon.

13. 2. Missense mutation / 错义突变 错义突变：引起蛋白质中一个氨基酸变化的点突变。 Missense mutation:A point mutation that causes a change in one amino acid of a protein.

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

15. 3. Nonsense mutation / 无义突变 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。 Nonsense mutation:A point mutation that introduces a stop codon before the normal stop codon of the gene.

16. Q2→ 9.5.2 What consequences do insertions and deletions have?插入和缺失会有什么后果？

17. A2→ Frameshift mutation / 移码突变 移码突变：一种引起mRNA读码框位置发生变化的突变，通常由插入和缺失引起。 Frameshift mutation: A mutation that causes a shifting of the reading frame of an mRNA. It is generally caused by insertions and deletions. 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。 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.

18. Frameshift mutation / 移码突变

19. “The cat ate its rat.” “Txh eca tat eit sra t.” “The cat ate its rat.” hpcsc.appstate.edu/index.php? module=pagemaste... 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。

20. Q3→ What consequences do translocations have? 易位会有什么后果？

21. 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

22. Chronic myelogenous leukemia慢性骨髓性白血病 biomed.brown.edu/Courses/ BI279/Lec12/Lec12-D.htm spsingh.net/

23. A3→ Translocation may result in the formation of fusion gene / 易位会导致产生融合基因 融合基因：通过融合两个或多个不同基因产生的基因 Fusion gene:A gene that is formed by fusing together two or more different genes.

24. What causes CML? 异常基因 Bcr-Abl 骨髓中产生过 多的白细胞 Bcr-Abl 酪氨酸激酶

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

26. What causes Burkitt’s lymphoma? c-myc

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

28. Q4→ 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

29. A4→ 9.5.4 Mutation Hot Spots / 突变热点 突变热点：比其它位点更容易发生突变的DNA位点. Mutation hot spots:Specific DNA sites that are more likely to occur mutation than other sites. A mutation hot spot

30. Mutation Hot Spots / 突变热点

31. 9.6 Mutation Repair / 突变修复

32. Mutation Repair / 突变修复

33. Q5→ How can damage on DNA be repaired? DNA损伤如何被修复呢？

34. A5-1→ 9.6.1 Direct Reversal / 直接回复 Photolyase Visible light . . . . . . T C A T T G C C A G T A A C G G UV light 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）

35. A5-2→ 9.6.2 Mismatch Repair / 错配修复 错配修复：一种用于修复DNA分子中错配碱基的机理。 Mismatch repair:A mechanism used for the repair of mismatched bases in a DNA molecule. 错配修复（MMR）特异性地将目标放在子链中错配的碱基上。基因组中的GATC序列提供了一种区别母链和子链的便利途径，因为在新链合成出来后的几分钟时间内A还保持着未甲基化的状态。

36. MMR: Mismatch Repair (1/2)

37. MMR: Mismatch Repair (2/2)

38. A5-3→ 9.6.3 Nucleotide Excision Repair 核苷酸切除修复 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。 Nucleotide excision repair:A kind of excision repair usually used to fix nucleotides that have undergone large or unusual modifications.

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

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

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

42. Now showingOverview of Eukaryotic Gene Expression File: biophoto7 \Genetics: A Conceptual Approach \ Overview of eukaryotic gene expression (15’)

43. Essentials of Lecture 24 / 第24讲要点 A1→ Consequences of Point Mutations 点突变的后果 A2→ Frameshift mutation / 移码突变 A3→ Translocation may result in the formation of fusion gene 易位会导致产生融合基因 A4→ Mutation Hot Spots / 突变热点 A5-1→ Direct Reversal / 直接回复 A5-2→ Mismatch Repair / 错配修复 A5-3→ Nucleotide Excision Repair 核苷酸切除修复

44. A1→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

45. A2→ Frameshift mutation / 移码突变 移码突变：一种引起mRNA读码框位置发生变化的突变，通常由插入和缺失引起。 Frameshift mutation: A mutation that causes a shifting of the reading frame of an mRNA. It is generally caused by insertions and deletions. 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。 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.

46. A3→ Translocation may result in the formation of fusion gene / 易位会导致产生融合基因 融合基因：通过融合两个或多个不同基因产生的基因 Fusion gene:A gene that is formed by fusing together two or more different genes.

47. A4→ 9.5.4 Mutation Hot Spots / 突变热点 突变热点：比其它位点更容易发生突变的DNA位点. Mutation hot spots:Specific DNA sites that are more likely to occur mutation than other sites. A mutation hot spot

48. A5-1→ 9.6.1 Direct Reversal / 直接回复 Photolyase Visible light . . . . . . T C A T T G C C A G T A A C G G UV light 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）

49. A5-2→ 9.6.2 Mismatch Repair / 错配修复 错配修复：一种用于修复DNA分子中错配碱基的机理。 Mismatch repair:A mechanism used for the repair of mismatched bases in a DNA molecule. 错配修复（MMR）特异性地将目标放在子链中错配的碱基上。基因组中的GATC序列提供了一种区别母链和子链的便利途径，因为在新链合成出来后的几分钟时间内A还保持着未甲基化的状态。

50. A5-3→ 9.6.3 Nucleotide Excision Repair 核苷酸切除修复 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。 Nucleotide excision repair:A kind of excision repair usually used to fix nucleotides that have undergone large or unusual modifications.