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Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein DinB
Author(s) -
Ogi Tomoo,
Kato Tomohisa,
Kato Takesi,
Ohmori Haruo
Publication year - 1999
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1999.00289.x
Subject(s) - biology , frameshift mutation , mutagenesis , gene , escherichia coli , genetics , dna polymerase , mutation , saccharomyces cerevisiae , microbiology and biotechnology , dna
Background The Escherichia coli dinB gene is an SOS gene known to be required for λ 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.