title: Genotoxic stress-mediated cell cycle activities for the decision of cellular fate.
abstract: Genomic integrity maintenance is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Coupled with normal replication, the local intracellular and extracellular stresses cause damage to cellular DNA that is recognized and repaired by the DNA damage response (DDR) pathway. p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage, and thus participates in maintaining genome stability. p53 and many other anti-proliferative factors such as TGF beta regulate the expression of different cyclin-dependent kinase inhibitors (CDKIs). Paradoxically, one of the cellular proliferative factors, c-Myc proto-oncogene also controls the expression of these CDKIs and modulates the fate of cell in response to DNA damage. Furthermore, involvement of numerous other proteins in the DDR and crosstalk between them are likely to substantiate the DDR as one of the genome's most extensive signaling networks. Versatile protein kinases in this network affect the decision about four basic cellular fates, which are quiescence, apoptosis, oncogenesis and senescence, in response to DNA damage.
authors.affiliation: Erol Project Development House for the Disorders of Energy Metabolism, Silivri, Istanbul, Turkey. eroladnan@hotmail.com
authors.forename: Adnan
authors.initials: A
authors.lastname: Erol
mesh_terms: D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases