Yadi Zhou 20131205 RecA protein 38 kiloDalton Essential for the repair and maintenance of DNA A RecA structural and functional homolog has been found in every species Homologous protein in ID: 811347
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Slide1
Role of RecA in DNA replication
Yadi
Zhou
2013.12.05
Slide2RecA protein38 kiloDaltonEssential for the repair and maintenance of DNAA RecA structural and functional homolog has been found in every speciesHomologous protein in
Homo sapiens
is RAD51
Important enzyme in
homologous
recombination
Induce SOS response
Slide3Structure
Slide4RecA filament
RecA-dsDNA
Slide5Homologous recombination
Slide6Homologous recombination
Slide7SOS response
Slide8E. coli strains deficient in RecA are useful
Potential drug
target
Slide9Referenceshttp://www.callutheran.edu/BioDev/omm/reca/recamast.htmhttp://en.wikipedia.org/wiki/RecANature Reviews Molecular Cell Biology 8, 127-138 (February 2007)http://www.callutheran.edu/BioDev/omm/reca/recamast.htmNature 453, 463-466(22 May 2008)
Slide10Thank you!
Slide11Mechanisms of RecA DNA RepairVivian LesendeDecember 5, 2013BIOS 7200
Slide12Can arrest replication --- deletions/genomic rearrangements, point mutations, lethalityMany types of lesions can inhibit normal progression of replication forks-UV radiation – cis, syn-cyclobutane pyrimidine dimer (CPD) & pyrimidine-6-4-pyrimidone photoproduct (6-4 PP)DNA Damage
Slide13RecA functions to recover replication forks in several different ways-acts as transactivator for upregulating over 40 genes (SOS response)-protects single stranded DNA from degradation while replication is arrested-promotes recombination repair
RecA
Functions
Slide14LexA -- repressor binds to a 20 bp consensus sequence in operator region in DNA-damage inducible genesRecA bound to damaged single stranded DNA causes autocatalytic cleavageIncreases transcription of genes involved in SOS ResponseSOS Response
Slide15Genes that function to remove lesions and restore replicationuvrA & uvrB -- recognize UV-induced lesionsydjQ (cho) -- incision step for excision repairpolB, dinB
,
umuC
&
umuD
– DNA polymerases Pol II,
PolI
V, Pol V
Genes Involved in SOS Response
Slide16SOS ResponseCourcelle & Hanawalt
.
Annu
. Rev. Genet. 2003. 37:611-46
Slide17RecA maintains structure of replication forks until replication resumesAllows for nucleotide excision repair to occurrecA mutants have high sensitivity to UV-light – “rec-less” degradationPrevention of Degradation of Single-Stranded DNA of Replication Forks
Slide18Prevention of Degradation of Single-Stranded DNA of Replication ForksCourcelle
&
Hanawalt
.
Annu
. Rev. Genet. 2003. 37:611-46
Slide19“postreplication repair” or “daughter-strand gap repair”RecA promotes recombination as an alternative to excision repair – does not remove lesions from DNATypically only occurs if previous mechanisms have failedRecombination Recovery
Slide20Recombination RecoveryCourcelle & Hanawalt.
Annu
. Rev. Genet. 2003. 37:611-46
Slide21J. Courcelle & P. C. Hanawalt. RecA-Dependent Recovery of Arrested DNA Replication Forks. Annu. Rev. Genet. 2003. 37:611-46References