1. Mechanism of Homologous Recombination
MCB 720
Yahan wei

2. Outline Background information
Mechanisms of Homologous Recombination (HR)
Reference

3. What is HR?
Exchange of nucleotide sequences between two similar or identical DNA molecules
in mitosis: repair double-stand breaks (DSB) –DNA repair
in meiosis: provide new combinations of DNA sequences –DNA mutation

4. How it was discovered?
1860s Gregor Mendel –the principles of inheritance
Early 1900s William Bateson and Reginald Punnett –some genes can be inherited together
1911 Thomas Hunt Morgan –crossover can occur between linked genes
Around 1930 Barbara McClintock and Harriet Creighton –crossover happens both in meiosis and mitosis
1947 Joshua Lederberg found recombination in bacteria
1964 Robin Holliday –Holliday Junction
1983 Jack Szostak –DSBR pathway
………………
Common phenomenon
Present in the three domains of life

5. Initiation of HR
Meiotic recombination is initiated by programmed double-stand breaks by Spo11 complex on hotspots
Endonucleases involved to generate 3’ ss-DNA

6. Initiation of HR Recombinase as RecA/ Rad51/ Dmc1 bind to the ss-DNA
Accessory factors as Rad54, Rad54B, and Rdh54 help recognize and invade the homologous region

7. Initiation of HR
After the formation of D-loop, DNA polymerase involved to elongate the 3’ invading single strand

8. DSBR & SDSA pathways
Crossover
Non-crossover

9. Holliday Junction

10. Action of recombination mediators
Compared with Rad51, RPA (Replication Protein A) has higher ssDNA binding affinity
Recombination mediators helps Rad51 binds to ssDNA

11. Regulation of recombination
If crossover happens among repetitive DNA sequences, chromosome translocation can occur.
HR can also interfere post-replication repair, which result into prolonged activation of DNA-damage checkpoint-mediated cell cycle arrest.

12. Regulation of recombination

13. Application of HR
Knockout genes: generate trans-genetic animals, plants, or microorganisms

14. Reference
Patrick Sung and Hannah Klein (2006). Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nature Reviews Mol.Cell Biol. 7,
Lodish et al., (2007) Molecular Cell Biology, 6th, W.H. Freeman and Company
Jeremy M. Berg (2007) Biochemistry 6th, W.H. Freeman and Company

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Thank you!