武汉大学分子生物学课件考研复习

The Holliday model illustrates key steps in homologous recombination
The Holliday model very well illustrates the DNA strand invasion, branch migration, and Holliday junction resolution processes central to homologous recombination. (Figures 10-1 and 10-2)
Programmed generation of double –stranded DNA breaks occurs during meiosis
1. The Spo11 protein introduces DSBs in chromosomal DNA at many locations to initiate meiotic recombination. 2. SPO11 gene is expressed specifically during meiosis, and Spo11-mediated DNA cleavage occurs right around the time when the replicated homologous chromosomes start to pair.
3/29/05
Different changes of DNA sequences Listen to the nature



Mutation is bad and naturally repaired, thus it could not be responsible for biodiversity. Recombination is good and naturally promoted; it is responsible for diversity inside of species. Transposition is different from mutation and recombination because (1) producing mechanism is different; (2) no mechanism to correct it; (3) existing in nature in a well-controlled manner (10-5). Not repaired but controlled.
The duplicated homologous chromosomes must pair. *** Without recombination, chromosome often fails to align properly for the first meiotic division.
Fra Baidu bibliotek
Figure 10-14 DNA dynamics during meiosis
•Molecular Biology Course
CHAPTER 10 Homologous recombination at the molecular level
All DNA is recombinant DNA. Genetic exchange works constantly to blend and rearrange chromosomes, most obviously during meiosis, when homologous chromosomes pair prior to the first nuclear division. During this pairing, genetic exchange between the chromosomes occurs. This exchange, classically termed crossing over, is one of the results of homologous recombination.
Topic 2: Homologous recombination protein machines---RecBCD pathway
1. RecBCD helicase/nuclease processes broken DNA ends for recombination ( site). 2. RecA protein promotes strand invasion (how?). 3. RuvAB complex promotes branch migration. 4. RuvC resolves the Holliday junction
Part III: Expression of the Genome
Part IV: Regulation Part V: Methods
3/29/05
Part II: Maintenance of the Genome
Dedicated to the structure of DNA and the processes that propagate, maintain and alter it from one cell generation to the next
CHAPTER 10 Homologous recombination at the molecular level
Topic 1: Models for Homologous Recombination
1.Holliday model (Holliday模型) 2.Double-strand break (DSB) repair model (双链断裂修复模型)
Key steps shared by different models Alignment (结盟) of two homologous DNA molecules. Introduction of breaks in the DNA Formation of initial short regions of base pairing between the two recombining DNA molecules: strand invasion Movement of the Holliday junction: branch migration Cleavage of the Holliday junction: resolution
Watch the animation for details!
CHAPTER 10 Homologous recombination at the molecular level
Topic 3: Homologous recombination in eukaryotes
Biological functions of homologous recombination in eukaryotes

1.
OUTLINE
2.
3.
4. 5.
Models for Homologous Recombination (two models)** Homologous Recombination Protein Machines (RecBCD pathway)** Homologous Recombination in Eukaryotes (meiosis recombination, proteins) Mating-Type Switching (a gene conversion event) Genetic Consequences of the Mechanism of Homologous Recombination (exchange or conversion)
Ch 6: The structures of DNA and RNA Ch 7: Chromosomes, chromatins and the nucleosome Ch 8: The replication of DNA Ch 9: The mutability and repair of DNA Ch 10: Homologous recombination at the molecular level Ch 11: Site-specific recombination and transposition of DNA
(复制叉瓦解)
Figure 10-4. Damage
in the DNA template can lead to DSB formation during replication
CHAPTER 10 Homologous recombination at the molecular level
Watch the animation for details!
The double-strand break repair model more accurately describes many recombination events
1.
2.
Homologous recombination is often initiated by double-stranded breaks (DSB) in DNA, while Holliday model is initiate by the pair of aligned nicks. DSB occurs relatively frequently, but the aligned nicks not.
1. Critical for DNA repair and the restarting of collapsed (瓦解的) replication forks. 2. During meiosis, homologous recombination is Required for proper chromosome pairing, thus for maintaining the integrity of the genome.
Double –stranded DNA breaks arise by numerous means and initiate homologous recombination
1.
2.
3.
DSBs in DNA arise quite frequently. In bacteria, the major biological role of homologous recombination is to repair DSBs (Ionizing radiation, damage in the DNA template); DSBs also promotes genetic exchange. In eukaryotic cells, homologous recombination is critical for DNA repairing, as well as for the process of chromosomal pairing during meiosis.
DSB breaks Processing of the DSB to generate DNA with 3’ ss tails Strand invasion of 3’ end
Second strand invasion and DNA repair synthesis from the 3’ ends Branch formation and migration Figure 10-3 DSB repair model
Welcome Each of You to My Molecular Biology Class
Molecular Biology of the Gene, 5/E --- Watson et al. (2004)
Part I: Chemistry and Genetics
Part II: Maintenance of the Genome