Mismatch Repair-Dependent Transcriptome Changes In Human Cells Treated with the Methylating Agent N-Methyl-N′-Nitro-N-Nitrosoguanidine

摘要: DNA mismatch repair (MMR) plays a key role in the cytotoxic response of human cells to methylating agents, however, cascade events leading cell cycle arrest and death has yet be characterized. We studied MMR transcriptional methylation damage two cellular models: (a). lymphoblastoid line TK6 its derivative MT1, which is mutated gene hMSH6; (b). epithelial 293T Lalpha expression hMLH1 can tightly regulated p53 inactivated. Upon N-methyl-N'-nitro-N-nitrosoguanidine treatment, only with functional were killed, but type differed. In cells, S-phase apoptosis accompanied by dramatic change expression, notably, an up-regulation several genes encoding growth inhibitors proapoptotic factors both dependent independent. contrast, MMR-dependent was substantially less pronounced than despite efficient induction G(2)-M checkpoint nonapoptotic death. Thus, we demonstrate that different origin, MMR-mediated killing agents occurs through pathways regardless status. Moreover, once been processed system, tumor might committed die, although one or more their signaling are impaired.