Multiple transcription factors regulate the expression of genes for error prone DNA polymerases in Acinetobacter baumannii
Brian H. Nguyen, Carly ChingiD, Ashley Erin MacGuire, Pranav Casula, Connor Newman, Faith Finley, Veronica G. Godoy
Abstract
Acinetobacter baumannii is an opportunistic pathogen causing several infections that are increasingly diSicult to treat due to its ability to rapidly gain antibiotic resistances. These resistances can arise due to mutations during the DNA damage response (DDR), through the activity of error-prone DNA polymerases, such as DNA polymerase V (DNA Pol V). Currently, the DDR in A. baumannii is not well understood and the regulation of genes encoding multiple copies of DNA Pol V is not fully characterized. Through genome wide mutagenesis, we have identified a novel TetR-like family regulator of genes that encode DNA Pol V, which we have named Error-prone polymerase regulator, EppR. We have found that EppR represses the expression of the genes encoding DNA Pol V and itself through direct binding to a conserved EppR motif in their promoters. Lastly, we show that EppR also regulates UmuDAb, previously identified as a regulator of genes encoding DNA Pol V. These two gene products are functionally required to ensure regulation of expression of genes encoding DNA Pol Vs and umuDAb. With these results, we propose a co-repressor model for the regulation of genes encoding DNA Pol V and umuDAb. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/615892v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@502a49org.highwire.dtl.DTLVardef@10844bcorg.highwire.dtl.DTLVardef@1d8be41org.highwire.dtl.DTLVardef@b2a68e_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
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