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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
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10.1 Homologous Recombination 同源重组
Diploid (2n)2 copies of eachchromosome
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Homologous Recombination
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If these chromosomes were left unchanged …
Child
Grand-child
Identical
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Crossing-over in meiosis
Child
Grand-child
Different
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Homologous Recombination in DNA repair
Homologouschromosomes
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10.1.1 Mechanism for Crossing-Over / 交换机理
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Mechanism of recombination in yeast (1/2)
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Mechanism of recombination in yeast (2/2)
Holliday junctions
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Branch migration of Holliday junctionsHolliday 交叉的分支迁移
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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
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Resolution of the Holliday junctionto create a crossover
产生交换的 Holliday 交叉拆分
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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’
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Resolution of Holliday junctionsfor non-crossover
不产生交换的 Holliday 交叉拆分
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Brca1/Brca2 deletion and breast cancer Brca1/Brca2 缺失与乳腺癌
www.harthosp.org/cancer/breast.htm
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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
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Now showing
Meselson-Radding Heteroduplex Model
File: biophoto7 \ Introduction to Genetic Analysis \ Meselson-Radding heteroduplex Model
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10.1.3 The RecBCD Pathway (1/3)
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The RecBCD Pathway (2/3)
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The RecBCD Pathway (3/3)
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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’
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Gene Conversion / 基因转换
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Gene Conversion / 基因转换
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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
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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
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Now showing
Gene Conversion
File: biophoto7 Introduction to Genetic Analysis Genetic Consequences of Meselson-Radding Model
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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
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10.2.1 Transposons / 转座子
GGTACTCTCCCCATGAGAGG
AATCGCGGTTAGCGCC
CCGCGATTGGCGCTAA
GGTACTCTCCCCATGAGAGG
Insertion sequence
Direct repeats
Inverted repeats
Genes codingfor transposase
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Transposition / 转座
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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
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Now showing
Replicative transposition
File: biophoto7 \ Introduction to Genetic Analysis \ Replicative transposition. (5’)
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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
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LTR-RetrotransposonsLTR 反转录转座子
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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
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10.2.3 Bacteriophage λ integrationλ 噬菌体的整合
Lysis Lysogeny
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Phage integration and excision
attP: attachment sites of phageattB: attachment sites of bacterium