Mechanism of Homologous Recombination MCB 720 Yahan wei

Outline Background information Mechanisms of Homologous Recombination (HR) Reference

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

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

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

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

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

DSBR & SDSA pathways Crossover Non-crossover

Holliday Junction

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

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.

Regulation of recombination

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

Reference Patrick Sung and Hannah Klein (2006). Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nature Reviews Mol.Cell Biol. 7, 739-750. http://en.wikipedia.org/wiki/Homologous_recombination 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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