TY - JOUR

T1 - A critical role for the putative NCS2 nucleobase permease YjcD in sensitivity of Escherichia coli to cytotoxic and mutagenic purine analogs

AU - Kozmin, S.G.

AU - Stepchenkova, E.I.

AU - Chow, S.C.

AU - Schaaper, R.M.

PY - 2013

Y1 - 2013

N2 - The base analogs 6-N-hydroxylaminopurine (HAP) and 2-amino-HAP (AHAP) are potent mutagens in bacteria and eukaryotic organisms. Previously, we demonstrated that a defect in the Escherichia coli ycbX gene, encoding a molybdenum cofactor-dependent oxidoreductase, dramatically enhances sensitivity to the toxic and mutagenic action of these agents. In the present study, we describe the discovery and properties of a novel suppressor locus, yjcD, that strongly reduces the HAP sensitivity of the ycbX strain. Suppressor effects are also observed for other purine analogs, like AHAP, 6-mercaptopurine, 6-thioguanine, and 2-aminopurine. In contrast, the yjcD defect did not affect the sensitivity to the pyrimidine analog 5-fluorouracil. Homology searches have predicted that yjcD encodes a putative permease of the NCS2 family of nucleobase transporters. We further investigated the effects of inactivation of all other members of the NCS2 family, XanQ, XanP, PurP, UacT, UraA, RutG, YgfQ, YicO, and YbbY, and of the NCS1 famil

AB - The base analogs 6-N-hydroxylaminopurine (HAP) and 2-amino-HAP (AHAP) are potent mutagens in bacteria and eukaryotic organisms. Previously, we demonstrated that a defect in the Escherichia coli ycbX gene, encoding a molybdenum cofactor-dependent oxidoreductase, dramatically enhances sensitivity to the toxic and mutagenic action of these agents. In the present study, we describe the discovery and properties of a novel suppressor locus, yjcD, that strongly reduces the HAP sensitivity of the ycbX strain. Suppressor effects are also observed for other purine analogs, like AHAP, 6-mercaptopurine, 6-thioguanine, and 2-aminopurine. In contrast, the yjcD defect did not affect the sensitivity to the pyrimidine analog 5-fluorouracil. Homology searches have predicted that yjcD encodes a putative permease of the NCS2 family of nucleobase transporters. We further investigated the effects of inactivation of all other members of the NCS2 family, XanQ, XanP, PurP, UacT, UraA, RutG, YgfQ, YicO, and YbbY, and of the NCS1 famil

U2 - 10.1128/mBio.00661-13

DO - 10.1128/mBio.00661-13

M3 - Article

VL - 4

JO - mBio

JF - mBio

SN - 2150-7511

IS - 6

M1 - e00661

ER -