Cells deficient in base-excision repair reveal cancer hallmarks originating from adjustments to genetic instability

摘要: Genetic instability, provoked by exogenous mutagens, is well linked to initiation of cancer. However, even in unstressed cells, DNA undergoes a plethora spontaneous alterations its inherent chemical instability and the intracellular milieu. Base excision repair (BER) major cellular pathway responsible for these lesions, as deficiency BER activity results damage it has been proposed that may trigger development sporadic cancers. Nevertheless, experimental evidence this model remains inconsistent elusive. Here, we performed proteomic analysis deficient human cells using stable isotope labelling with amino acids cell culture (SILAC), demonstrate deficiency, which induces genetic dramatic changes gene expression, resembling found many We observed profound tissue homeostasis, serine biosynthesis, one-carbon- acid metabolism, all have identified cancer ‘hallmarks’. For first time, study describes expression characteristic endogenous lesions BER. These resemble those suggesting genetically unstable be source pre-cancerous cells.