Thymineless death is inhibited by CsrA in Escherichia coli lacking the SOS response.
Thymineless death (TLD) is the rapid loss of colony-forming ability in bacterial, yeast and human cells starved for thymine, and is the mechanism of action of common chemotherapeutic drugs. In Escherichia coli, significant loss of viability during TLD requires the SOS replication-stress/DNA-damage response, specifically its role in inducing the inhibitor of cell division, SulA. An independent RecQ- and RecJ-dependent TLD pathway accounts for a similarly large additional component of TLD, and a third SOS- and RecQ/J-independent TLD pathway has also been observed. Although two groups have implicated the SOS-response in TLD, an SOS-deficient mutant strain from an earlier study was found to be sensitive to thymine deprivation. We performed whole-genome resequencing on that SOS-deficient strain and find that, compared with the SOS-proficient control strain, it contains five mutations in addition to the SOS-blocking lexA(Ind(-)) mutation. One of the additional mutations, csrA, confers TLD sensitivity specifically in SOS-defective strains. We find that CsrA, a carbon storage regulator, reduces TLD in SOS- or SulA-defective cells, and that the increased TLD that occurs in csrA(-) SOS-defective cells is dependent on RecQ. We consider a hypothesis in which the modulation of nucleotide pools by CsrA might inhibit TLD specifically in SOS-deficient (SulA-deficient) cells.
Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology and the Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030-3411, United States.
Holly M
HM
Hamilton
Ray
R
Wilson
Martin
M
Blythe
Ralf B
RB
Nehring
Natalie C
NC
Fonville
Edward J
EJ
Louis
Susan M
SM
Rosenberg
D001426:Bacterial Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D016680:Genome, Bacterial; D050296:Microbial Viability; D020125:Mutation, Missense; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013014:SOS Response, Genetics; D012697:Serine Endopeptidases / Q000378:metabolism; D013941:Thymine / Q000378:metabolism*; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D012697:Serine Endopeptidases; D013941:Thymine; D000099160:LexA Repressor Protein; C093587:CsrA protein, E coli
DNA damage response; DNA repair; RecQ; SOS response; Thymineless death; csrA