yadi zhou 2013.12.05. reca protein 38 kilodalton essential for the repair and maintenance of dna a...
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Role of RecA in DNA replication
Yadi Zhou
2013.12.05
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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 Homo sapiens is RAD51
• Important enzyme in homologous recombination• Induce SOS response
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Structure
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RecA filament
RecA-dsDNA
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Homologous recombination
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Homologous recombination
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SOS response
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• E. coli strains deficient in RecA are useful
• Potential drug target
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References
• http://www.callutheran.edu/BioDev/omm/reca/recamast.htm• http://en.wikipedia.org/wiki/RecA• Nature Reviews Molecular Cell Biology 8, 127-138
(February 2007)• http://www.callutheran.edu/BioDev/omm/reca/
recamast.htm• Nature 453, 463-466(22 May 2008)
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Thank you!
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Mechanisms of RecA DNA Repair
Vivian LesendeDecember 5, 2013
BIOS 7200
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• Can arrest replication --- deletions/genomic rearrangements, point mutations, lethality• Many 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
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• RecA 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
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• LexA -- repressor binds to a 20 bp consensus sequence in operator region in DNA-damage inducible genes• RecA bound to damaged single stranded DNA
causes autocatalytic cleavage• Increases transcription of genes involved in SOS
Response
SOS Response
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• Genes that function to remove lesions and restore replication• uvrA & uvrB -- recognize UV-induced lesions• ydjQ (cho) -- incision step for excision repair• polB, dinB, umuC & umuD – DNA polymerases Pol II,
PolI V, Pol V
Genes Involved in SOS Response
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SOS Response
Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46
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• RecA maintains structure of replication forks until replication resumes• Allows for nucleotide excision repair to occur• recA mutants have high sensitivity to UV-light –
“rec-less” degradation
Prevention of Degradation of Single-Stranded DNA of Replication Forks
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Prevention of Degradation of Single-Stranded DNA of Replication Forks
Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46
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• “postreplication repair” or “daughter-strand gap repair”• RecA promotes recombination as an alternative to
excision repair – does not remove lesions from DNA• Typically only occurs if previous mechanisms have
failed
Recombination Recovery
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Recombination Recovery
Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46
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• J. Courcelle & P. C. Hanawalt. RecA-Dependent Recovery of Arrested DNA Replication Forks. Annu. Rev. Genet. 2003. 37:611-46
References