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

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

UV irradiation lesions

• cis, syn-cyclobutane pyrimidine dimer (CPD)

• pyrimidine-6-4-pyrimidone photoproduct (6-4 PP)

Other Key Genes

• LexA repressor • uvrA, uvrB, and uvrC• ydjQ (now termed cho)• polB, dinB, and umuC plus umuD

Regulation of SOS genes by RecA/LexA

Recovery by Recombination

Questions remained…

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

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.

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.

Model is revised

Repair-by-recombination model

Repair-without-recombination model: RecA simply maintains the fork until replication

can resume.

Recovery without Recombination

Recovery without Recombination

Experiments to support the model

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.