The role of SOS and flap processing in microsatellite instability in Escherichia coli.
Mutations affecting mismatch repair result in elevated frequencies of microsatellite length alteration in prokaryotes and eukaryotes. However, the finding that microsatellite instability is found often in cells with a functional mismatch repair system prompted a search for other factors of tract alteration. In the present report, we show that, in Escherichia coli, poly(AC/TG) tracts are destabilized by mutations that induce SOS. These observations may have implications for eukaryotic cells because recent results suggest the existence of a mammalian SOS response analogous to that in prokaryotes. In addition, a defect in the 5'-3' exonuclease domain of DNA polymerase I, homologous to the mammalian FEN1 and the yeast RAD27 nucleases, leads to a marked increase in repeat expansions characteristic of several genetic disorders. Finally, we found that the combination of a proofreading defect with mismatch repair deficiency results in extreme microsatellite instability.
Génétique Microbienne, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France.
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P
Morel
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C
Reverdy
B
B
Michel
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Ehrlich
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Cassuto
D000818:Animals; D001483:Base Sequence; D000071877:Checkpoint Kinase 1; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D018900:Dinucleotide Repeats; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D045585:Flap Endonucleases; D016368:Frameshift Mutation; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics; D011995:Recombination, Genetic; D013014:SOS Response, Genetics
D017931:DNA Primers; D004269:DNA, Bacterial; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases