英漢對照分子生物學(xué)導(dǎo)論-Chapter-9課件

1、1 / 81Chapter 9 / 第第9章章Chapter 9 Mutations and Mutation Repair9.1 DNA Damage and Mutations9.2 Point Mutations9.3 Insertions and Deletions9.4 Large-Scale DNA changes9.5 Consequences of DNA Mutations9.6 Mutation Repair9.7 Experiments第9章 突變與 突變修復(fù)9.1 DNA損傷與突變9.2 點突變9.3 插入和缺失9.4 大規(guī)模DNA變化9.5 DNA突變的后果9.6 突

2、變修復(fù)9.7 實驗研究2 / 81Mutations and Mutation Repair突變與突變修復(fù)突變與突變修復(fù)Chemicals化學(xué)物質(zhì)Radiation輻射Transposons轉(zhuǎn)座子Replicationerrors復(fù)制錯誤3 / 819.1 DNA Damage and MutationsDNA損傷與突變損傷與突變A heritable change in DNA sequence is called a mutation. Most frequently, the word mutation is applied to heritable alterations that a

3、ffect the function of a gene. DNA序列中可遺傳的改變稱為突變。大多數(shù)時候突變一詞用來指影響到基因功能的可遺傳改變。4 / 81Mutation can be favorable突變可以是有利的突變可以是有利的MUTAtiOn5 / 819.2 Point Mutations / 點突變點突變Mutations affecting only one base pair are called point mutations. Usually, point mutations involve substitution of one base with another

4、base. If a pyrimidine is replaced with aother pyrimidine, or a purine by another purine it is called a transition. If a purine is replaced by a pyrimidine or vice-versa, it is called a transversion.只影響到一個堿基對的突變叫做點突變。通常，點突變涉及到一個堿基被另一個堿基替換。如果一個嘧啶被另一個嘧啶、或一個嘌呤被另一個嘌呤取代，這樣的點突變稱為轉(zhuǎn)換。如果一個嘌呤被一個嘧啶取代或反之，這樣的點突變稱

5、為顛換。6 / 81Transition vs. TransversionTCGATGGTTransition 轉(zhuǎn)換Transversion 顛換7 / 819.2.1 Mismatched Base / 錯配的堿基錯配的堿基d8 / 81Mismatched base Point mutation 9 / 819.2.2 Spontaneous Mutation / 自發(fā)突變自發(fā)突變1. Deamination / 脫氨基2. Depurination / 脫嘌呤3. Tautomerization / 互變異構(gòu)化10 / 811. Deamination / 脫氨基脫氨基CUReplica

6、tionG C A TUU11 / 812. Depurination / 脫嘌呤脫嘌呤AAATTTCCGGAAATTTCCGDepurinate( 5000 nt)Repair( most )12 / 81Depurination / 脫嘌呤脫嘌呤13 / 81Depurination Mutation“How can I continue my work?”DNA polAAATCG C A T C G T - A14 / 813. Tautomerization / 互變異構(gòu)化互變異構(gòu)化15 / 81Tautomeric forms of the DNA bases16 / 819.2.

7、3 Induced Mutations / 誘發(fā)突變誘發(fā)突變1. Base Analogues / 堿基類似物2. Alkylating Agents / 烷化劑3. Nitrous Acid / 亞硝酸4. Ultraviolet Radiation / 紫外輻射17 / 811. Base Analogues / 堿基類似物堿基類似物18 / 81BU* MutationA : TA : BUTautome-rizationA : BU*ReplicationG : BU*ReplicationA T G C19 / 812. Alkylating Agents / 烷化劑烷化劑Anoth

8、er class of molecules with the ability to cause point mutations is alkylating agent. These compounds can add alkyl groups to other molecules, including DNA bases. When aklylation changes base pairing properties, it will most likely lead to point mutations.能夠引起點突變的另一類分子是烷化劑。這些化合物能夠?qū)⑼榛拥狡渌肿由希拥紻NA的

9、堿基上。如果烷化作用改變了堿基的配對性質(zhì)，它就很可能會導(dǎo)致點突變。20 / 81EMS: ethylmethane sulfonate乙基甲磺酸乙基甲磺酸G : CmG : CEMSReplicationmG : TG C A T21 / 813. Nitrous Acid / 亞硝酸亞硝酸Pickled food腌制食品 Nitrous acid亞硝酸Cancer癌癥22 / 81Adenine Hypoxanthine腺嘌呤腺嘌呤 次黃嘌呤次黃嘌呤A : TH : THNO2ReplicationH : CA T G C23 / 81Cytosine Uracil胞嘧啶胞嘧啶 尿嘧啶尿嘧啶

10、C : GU : GHNO2ReplicationU : AC G T A24 / 814. Ultraviolet Radiation / 紫外輻射紫外輻射25 / 81Pyrimidine dimer / 嘧啶二聚體嘧啶二聚體26 / 81Cross-linking / 交聯(lián)交聯(lián) SCH2H2CH2CCH2ClCl芥子氣27 / 81Injuries caused by mustard /./onlinedisplay/1910s.html 28 / 819.3 Insertions and Deletions插入和缺失插入和缺失9.3.1 Strand

11、Slippage / 鏈滑動9.3.2 Transposons / 轉(zhuǎn)座子9.3.3 Intercalating Agents / 嵌入劑29 / 819.3.1 Strand Slippage / 鏈滑動鏈滑動30 / 81MSI: microsatellite instability微衛(wèi)星不穩(wěn)定性微衛(wèi)星不穩(wěn)定性/./MDGF/technology.shtml?MDGF Hereditary Non-PolyposisColorectal Cancer, HNPCC遺傳性非息肉型結(jié)腸癌31 / 819.3.2 Transposons / 轉(zhuǎn)座子轉(zhuǎn)座子Inse

12、rtions and deletions may also be caused by DNA elements called transposons. When a transposon relocates to another area of the genome it causes an insertion.插入和缺失也可能由稱為轉(zhuǎn)座子的DNA元件引起。當(dāng)轉(zhuǎn)座子再次定位到基因組的另一個區(qū)域時，它就會引起一個插入突變。32 / 819.3.3 Intercalating Agents / 嵌入劑嵌入劑A base pair33 / 81Intercalation Mutation34 / 8

13、19.4 Large-Scale DNA changes大規(guī)模大規(guī)模DNA變化變化Translocation / 易位35 / 81Inversion / 倒位倒位36 / 81Single-strand break / 單鏈斷裂單鏈斷裂Peroxides, Fe2+, Cu2+Ionizing radiationFree radicals37 / 81Double-strand break / 雙鏈斷裂雙鏈斷裂Other breaks38 / 81Repair of Double strand /heyerlab/Rooster.ht

14、m Extreme sensitivity to X-ray Moderate sensitivity to UV Hyper-sensitive tomethylmethane sulfonate Phenotypes caused by a RAD54 deletion 39 / 819.5 Consequences of DNA MutationsDNA突變的后果突變的后果11.5.1 Consequences of Point Mutations 點突變的后果11.5.2 Consequences of Insertions and Deletions 插入和缺失的后果11.5.3 C

15、onsequences of Translocations 易位的后果40 / 819.5.1 Consequences of Point Mutations / 點突變的后果點突變的后果1. Silent mutation 沉默突變2. Missense mutation 錯義突變3. Nonsense mutation 無義突變41 / 811. Silent mutation / 沉默突變沉默突變42 / 812. Missense mutation / 錯義突變錯義突變43 / 81Leaky mutation / 滲漏突變滲漏突變Normal redblood cellsSickle

16、 cells44 / 813. Nonsense mutation / 無義突變無義突變45 / 819.5.2 Consequences of Insertions and Deletions插入和缺失的后果插入和缺失的后果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.讀碼框：編碼區(qū)中堿基以三個一組形成的結(jié)構(gòu)，以起始密碼子和終止密碼子為開始和結(jié)束的標(biāo)志。46 /

17、81“The cat ate its rat.” “The cat ate its rat.” “Txh eca tat eit sra t.” /index.php?module=pagemaste. 47 / 81Frameshift mutation / 移碼突變移碼突變48 / 819.5.3 Consequences of Translocations易易 位位 的的 后后 果果Chronic myelogenous leukemia慢性骨髓性白血病 Burkitts lymphoma非洲淋巴瘤 49 / 81Chronic Myelogenous

18、 Leukemia慢性骨髓性白血病慢性骨髓性白血病 /Courses/BI279/Lec12/Lec12-D.htm 50 / 81What causes excess WBCs?51 / 81Burkitts lymphoma / 非洲淋巴瘤非洲淋巴瘤 www.gfmer.ch/./Maroua_case_presentation.htm 52 / 81What causes Burkitts lymphoma?53 / 81Function of gene c- Apoptosisbegins1234CelldividesCelldiesGene bci-2

19、Gene c-MycChromosome54 / 81Now showingOverview of Eukaryotic Gene ExpressionFile: biophoto7 Genetics: A Conceptual Approach Overview of eukaryotic gene expression (15)55 / 819.5.4 Mutation Hot Spots / 突變熱點突變熱點前方500米事故多發(fā)地段56 / 81Mutation Hot Spots / 突變熱點突變熱點57 / 819.6 Mutation Repair / 突變修復(fù)突變修復(fù)58 / 8

20、1Mutation Repair / 突變修復(fù)突變修復(fù)59 / 819.6.1 Direct Reversal / 直接回復(fù)直接回復(fù)UV lightVisible lightPhotolyaseT C A T T G C CA G T A A C G G. . . . . .光復(fù)活主要是原核生物中的一種修復(fù)方式。（遺傳學(xué)教材第451頁）60 / 819.6.2 Mismatch Repair / 錯配修復(fù)錯配修復(fù)61 / 81MMR: Mismatch Repair (1/2)62 / 81MMR: Mismatch Repair (2/2)63 / 8111.6.3 Nucleotide E

21、xcision Repair核苷酸切除修復(fù)核苷酸切除修復(fù)64 / 81NER: Nucleotide Excision Repair (1/2)65 / 81NER: Nucleotide Excision Repair (2/2)66 / 81MMR vs. NERMMR Mismatch NER Damaged bases67 / 819.6.4 Base Excision Repair堿基切除修復(fù)堿基切除修復(fù)Damage to C(e.g. deamination)68 / 81BER: Base Excision Repair (1/2)69 / 81BER: Base Excisio

22、n Repair (2/2)70 / 819.6.5 Double-Stranded Break Repair雙鏈斷裂修復(fù)雙鏈斷裂修復(fù)Extreme sensitivity to X-ray Moderate sensitivity to UV 71 / 81NHEJ: non-homologous end joining (1/3)72 / 81NHEJ: non-homologous end joining (2/3)73 / 81NHEJ: non-homologous end joining (3/3)74 / 81Homologous recombination同同 源源 重重 組組 75 / 819.7 Experiments / 實驗研究實驗研究11.7.1 Nucleotide Excision Repa