mechanism of homologous recombination mcb 720 yahan wei
Post on 21-Dec-2015
225 views
TRANSCRIPT
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 ………………
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
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.
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