Open AccessFrom single‐strand breaks to double‐strand breaks during S ‐phase: a new mode of action of the E scherichia coli C ytolethal D istending T oxin
Author(s) -
Fedor Y.,
Vignard J.,
NicolauTravers M.L.,
BoutetRobinet E.,
Watrin C.,
Salles B.,
Mirey G.
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12028
Subject(s) - cytolethal distending toxin , escherichia coli , homologous recombination , biology , dna damage , dna , genotoxicity , double strand , dna repair , homologous chromosome , cell cycle , microbiology and biotechnology , sos response , cell cycle checkpoint , apoptosis , genetics , gene , toxicity , chemistry , organic chemistry
Summary The C ytolethal D istending T oxin ( CDT ) is a genotoxin produced by several pathogenic bacteria. It is generally admitted that CDT induces double‐strand breaks ( DSB ) and cell cycle arrest in G 2/ M ‐phase, in an ATM ‐dependent manner. Most of these results were obtained at high dose (over 1 μg ml −1 ) of CDT and late after treatment (8–24 h). We provide here evidence that the E scherichia coli CDT ( EcCDT ) – at low dose (50 pg ml −1 or LD 50) and early after treatment (3–6 h) – progressively induces DNA DSB , mostly in S ‐phase. DSB formation is related to the single‐strand breaks induction by CDT , converted into DSB during the S ‐phase. We also show that homologous recombination is mobilized to these S ‐phase‐associated DSB . This model unveils a new mechanism for CDT genotoxicity that may play a role in cells partly deficient in homologous recombination.