41
1 / 41 Chapter 10 Recombination / 重 10.1 Homologous Recombinati on 10.1.1 Mechanism for Crossi ng-Over 10.1.2 Mechanism for Doubl e- Stranded Break R epair 10.1.3 The RecBCD pathway 10.1.4 Gene Conversion 10.2 Non-homologous Recombination 10.2.1 Transposons 10.1 重重重重 10.1.1 重重重重 10.1.2 重重重重 重重 重重 10.1.3 RecBCD 重重 10.1.4 重重重重 10.2 重重重重重 10.2.1 重重重 10.2.2 重重重重重重 10.2.3 λ 重重 重重

1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

Embed Size (px)

Citation preview

Page 1: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

1 / 41

Chapter 10 Recombination / 重组

10.1 Homologous Recombination

10.1.1 Mechanism for Crossing-Over

10.1.2 Mechanism for Double-

Stranded Break Repair

10.1.3 The RecBCD pathway

10.1.4 Gene Conversion

10.2 Non-homologous

Recombination

10.2.1 Transposons

10.2.2 Retrotransposons

10.2.3 Bacteriophage λ integration

10.1 同源重组 10.1.1 交换机理 10.1.2 双链断裂 修复机理 10.1.3 RecBCD 途径 10.1.4 基因转换

10.2 非同源重组

10.2.1 转座子 10.2.2 反转录转座子 10.2.3 λ 噬菌体的整合

Page 2: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

2 / 41

10.1 Homologous Recombination 同源重组

Diploid (2n)2 copies of eachchromosome

Page 3: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

3 / 41

Homologous Recombination

Page 4: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

4 / 41

If these chromosomes were left unchanged …

Child

Grand-child

Identical

Page 5: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

5 / 41

Crossing-over in meiosis

Child

Grand-child

Different

Page 6: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

6 / 41

Homologous Recombination in DNA repair

Homologouschromosomes

Page 7: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

7 / 41

10.1.1 Mechanism for Crossing-Over / 交换机理

Page 8: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

8 / 41

Mechanism of recombination in yeast (1/2)

Page 9: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

9 / 41

Mechanism of recombination in yeast (2/2)

Holliday junctions

Page 10: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

10 / 41

Branch migration of Holliday junctionsHolliday 交叉的分支迁移

Page 11: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

11 / 41

Resolution of the Holliday junctionHolliday 交叉的拆分

Resolution of the Holliday junctionto create a crossover产生交换的 Holliday 交叉拆分

Resolution of Holliday junctionsfor non-crossover不产生交换的 Holliday 交叉拆分

Page 12: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

12 / 41

Resolution of the Holliday junctionto create a crossover

产生交换的 Holliday 交叉拆分

Page 13: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

13 / 41

10.1.2 Mechanism for Double-Stranded Break Repair / 双链断裂修复机理

5’

3’

5’

3’

3’

5’

3’

5’

A double strand cut made by enzyme Spo11Chromosome A

Chromosome B

5’

3’

5’

3’

3’

5’

3’

5’

Page 14: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

14 / 41

Resolution of Holliday junctionsfor non-crossover

不产生交换的 Holliday 交叉拆分

Page 15: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

15 / 41

Brca1/Brca2 deletion and breast cancer Brca1/Brca2 缺失与乳腺癌

www.harthosp.org/cancer/breast.htm

Page 16: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

16 / 41

The roles of BRCA1 and BRCA2 in DNA repair BRCA1 和 BRCA2 在 DNA 修复中的作用

www-ermm.cbcu.cam.ac.uk/01003118h.htm

Page 17: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

17 / 41

Now showing

Meselson-Radding Heteroduplex Model

File: biophoto7 \ Introduction to Genetic Analysis \ Meselson-Radding heteroduplex Model

Page 18: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

18 / 41

10.1.3 The RecBCD Pathway (1/3)

Page 19: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

19 / 41

The RecBCD Pathway (2/3)

Page 20: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

20 / 41

The RecBCD Pathway (3/3)

Page 21: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

21 / 41

10.1.4 Gene Conversion / 基因转换

5’

3’

5’

3’

3’

5’

3’

5’

A double strand cut made by enzyme Spo11Chromosome A

Chromosome B

5’

3’

5’

3’

3’

5’

3’

5’

GTAT

GCAT

Homologous,Not identical.

3’5’

3’5’

3’5’

3’5’

Page 22: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

22 / 41

Gene Conversion / 基因转换

Page 23: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

23 / 41

Gene Conversion / 基因转换

Page 24: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

24 / 41

Neurospora crassa 粗糙脉孢菌

+

+m

m

Meiosis I减数分裂 I Meiosis II

减数分裂 II Mitosis有丝分裂

+

+

m

m

+

+

m

m

m

m

m

m

+

+

+

+

4 : 4

Page 25: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

25 / 41

Neurospora crassa 粗糙脉孢菌

www.nigms.nih.gov/Initiatives/Models/

www.neurosporagenome.org/

www.neurosporagenome.org/

4 : 4 5 : 3 6 : 2

Page 26: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

26 / 41

Now showing

Gene Conversion

File: biophoto7 Introduction to Genetic Analysis Genetic Consequences of Meselson-Radding Model

Page 27: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

27 / 41

10.2 Non-homologous Recombination非同源重组

10.2.1 Transposons 转座子

10.2.2 Retrotransposons 反转录转座子

10.2.3 Bacteriophage λ integration λ 噬菌体的整合

Page 28: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

28 / 41

10.2.1 Transposons / 转座子

GGTACTCTCCCCATGAGAGG

AATCGCGGTTAGCGCC

CCGCGATTGGCGCTAA

GGTACTCTCCCCATGAGAGG

Insertion sequence

Direct repeats

Inverted repeats

Genes codingfor transposase

Page 29: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

29 / 41

Transposition / 转座

Page 30: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair
Page 31: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

31 / 41

Generation of direct repeats同向重复序列的产生

GTACCATGATC

GATGGTACTAC

GTACCATGATCATGGTACTA

TACCATGATGATGGTACTAC

Insert transposon

Repair synthesis and seal gaps

Direct repeats

Page 32: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair
Page 33: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair
Page 34: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

34 / 41

Now showing

Replicative transposition

File: biophoto7 \ Introduction to Genetic Analysis \ Replicative transposition. (5’)

Page 35: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair
Page 36: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair
Page 37: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

37 / 41

10.2.2 Retrotransposons 反转录转座子

LTR-RetrotransposonsLTR 反转录转座子

Non-LTR Retrotransposons非 LTR 反转录转座子

Page 38: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

38 / 41

LTR-RetrotransposonsLTR 反转录转座子

Page 39: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

39 / 41

Non-LTR retrotransposons非 LTR 反转录转座子

p40

Transcription

AA- -A

AA- -A

Export

TranslationRNP assembly

━ AA- -A━EN RT

ORF1 ORF2

AA- -A

AA- -A

AA- -A

5’

5’

5’

5’

p40

ORF2

ORF2

T T- -T

Import or entry

during mitosis

?

━ AA- -A

Integration oftruncated L1at new chro-mosomal siteNucleus

Cytoplasm

Weaver’s Molecular Biology, 3rd Edition, Figure 23.31

Page 40: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

40 / 41

10.2.3 Bacteriophage λ integrationλ 噬菌体的整合

Lysis Lysogeny

Page 41: 1 / 41 Chapter 10 Recombination / 重组 10.1 Homologous Recombination 10.1.1 Mechanism for Crossing-Over 10.1.2 Mechanism for Double- Stranded Break Repair

41 / 41

Phage integration and excision

attP: attachment sites of phageattB: attachment sites of bacterium