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RecA-dependent recovery of arrested DNA replication forks
2012-10-30Chi Zhang Qiping Lu
Annu. Rev. Genet. 2003. 37:611–46 doi: 10.1146/annurev.genet.37.110801.142616
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Replication forks’ hurdles• abasic sites from spontaneous depurination• oxidative lesions such as thymine glycol and 8-
oxo-guanine• bulky chemical DNA adducts• photoproducts due to UV exposure• interstrand DNA crosslinks• ionizing radiation break single&double strand
DNA
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UV irradiation lesions
• cis, syn-cyclobutane pyrimidine dimer (CPD)
• pyrimidine-6-4-pyrimidone photoproduct (6-4 PP)
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Other Key Genes
• LexA repressor • uvrA, uvrB, and uvrC• ydjQ (now termed cho)• polB, dinB, and umuC plus umuD
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Regulation of SOS genes by RecA/LexA
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Recovery by Recombination
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Questions remained…
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Question # 1
Although RecA promoted limited survival in uvrA mutants, the survival of cells synergistically increased in the presence of excision repair.
If recA did promote DNA repair by recombination, it certainly did not operate with high efficiency in the absence of uvrA
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Question # 2
Observation: Replication was strongly inhibited by UV-induced DNA lesions, that the inhibition was more severe, and that replication failed to significantly recover in either recA or uvrA mutants.
Prediction from the recombinational model: Replication should continue at normal or near-normal rates through the lesion-containing parental DNA, leaving gaps at the lesion sites.
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Question # 3
Observation: Whenever significant levels of strand exchanges were detected in populations of cells, there was a corresponding high level of cell death and mutagenesis.
Prediction from the recombinational model: In the presence of DNA damage, the more strand exchanges that occur, the better off the cell should be.
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Model is revised
Repair-by-recombination model
Repair-without-recombination model: RecA simply maintains the fork until replication
can resume.
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Recovery without Recombination
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Recovery without Recombination
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Experiments to support the model
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Concluding remarksRecA was originally discovered as a gene required to change the genetic information during sexual cell cycles.
Now research have revealed that it is also the key enzyme required to maintain the genetic information when DNA damage is encountered during replication in asexual cell cycles.