Transcript Mechanism of homologous recombination

Mechanism of Homologous
Recombination
MCB 720
Yahan wei
Outline
Background information
 Mechanisms of Homologous
Recombination (HR)
 Reference

What is HR?
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Exchange of nucleotide
sequences between two
similar or identical DNA
molecules
in mitosis: repair doublestand breaks (DSB) –DNA
repair
in meiosis: provide new
combinations of DNA
sequences –DNA mutation
How it was discovered?
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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
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Initiation of HR
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Meiotic recombination
is initiated by
programmed doublestand breaks by
Spo11 complex on
hotspots
Endonucleases
involved to generate
3’ ss-DNA
Initiation of HR
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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
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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 checkpointmediated cell cycle arrest.
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Regulation of recombination
Application of HR
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Knockout genes:
generate transgenetic animals,
plants, or
microorganisms
Reference
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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
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Jeremy M. Berg (2007) Biochemistry 6th, W.H. Freeman
and Company
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