Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB.
BACKGROUND
The Escherichia coli dinB gene is an SOS gene known to be required for lambda phage untargeted mutagenesis. When over-expressed, it exhibits a potent mutagenic activity without any exogenous treatment to damage DNA. Frameshift mutations at a run of identical bases are most enhanced. The product DinB is structurally related to the E. coli UmuC protein and the Saccharomyces cerevisiae Rev1 and Rad30 proteins, all of which are shown to be involved in bypass synthesis at a DNA lesion.


RESULTS
We have cloned and sequenced human and mouse cDNAs encoding a DinB homologue. Their products are highly similar to DinB and less similar to UmuC, Rev1 or Rad30, and hence the genes were named DINB1 for human and Dinb1 for mouse. Both genes were expressed most abundantly in testis. Transient expression of the mouse cDNA in cultured mouse cells resulted in a nearly 10-fold increase in the incidence of point mutations, among which about 30% were frameshift mutations.


CONCLUSIONS
The above results suggest that a mutagenic mechanism, a so-called untargeted type, also operates in mammalian cells. Taken together with recent findings that human cells have multiple DNA polymerases for translesion synthesis which are homologous to the S. cerevisiae Rev3 and Rad30 proteins, our results imply that multiple mutagenic pathways are conserved from bacteria to higher eukaryotes.
Ogi
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Institute for Virus Research, Kyoto University, Kawahara-machi, Sakyo-ku, Kyoto 606-8507, Japan.
Kato
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Kato
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Ohmori
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H
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis; D004259:DNA-Directed DNA Polymerase; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000099270:Y-Family DNA Polymerases
D001426:Bacterial Proteins; D018076:DNA, Complementary; D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D007041:Hypoxanthine Phosphoribosyltransferase; D011506:Proteins; C094399:DinB protein, E coli; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases; C498613:Polk protein, mouse