期刊
CELLULAR MICROBIOLOGY
卷 15, 期 1, 页码 1-15出版社
WILEY
DOI: 10.1111/cmi.12028
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资金
- ANR programme [ANR-10-CESA-011]
- MYCA programme (Midi-Pyrenees region)
- French Ministry of Higher Education and Scientific Research
The Cytolethal Distending Toxin (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 G2/M-phase, in an ATM-dependent manner. Most of these results were obtained at high dose (over 1 mu g ml(-1)) of CDT and late after treatment (8-24 h). We provide here evidence that the Escherichia coli CDT (EcCDT) - at low dose (50 pg ml(-1) or LD50) 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.
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