Sensing, integrating, and processing of stressogenic signals must be followed by accurate differential response(s) for a cell to survive and avoid malignant transformation. The DNA damage response (DDR) pathway is vital in this process, as it deals with genotoxic/oncogenic insults, having p53 as a nodal effector that performs most of the above tasks. Accumulating data reveal that other pathways are also involved in the same or similar processes, conveying also to p53. Emerging questions are if, how, and when these additional pathways communicate with the DDR axis. Two such stress response pathways, involving the MKK7 stress-activated protein kinase (SAPK) and ARF, have been shown to be interlocked with the ATM/ATR-regulated DDR axis in a highly ordered manner. This creates a new landscape in the DDR orchestrated response to genotoxic/oncogenic insults that is currently discussed.

Danish Cancer Society Research Center; Copenhagen Denmark; Institute of Molecular and Translational Medicine; Faculty of Medicine and Dentistry; Palacky University; Olomouc Czech Republic

Faculty Institute of Cancer Sciences; University of Manchester; Manchester Academic Health Science Centre; Manchester UK; Manchester Centre for Cellular Metabolism; University of Manchester; Manchester Academic Health Science Centre; Manchester UK

Howard Hughes Medical Institute; Laboratory of Mammalian Cell Biology and Development; The Rockefeller University; New York NY USA

IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences; Vienna Austria

Molecular Carcinogenesis Group; Department of Histology and Embryology; School of Medicine; University of Athens; Athens Greece

Molecular Carcinogenesis Group; Department of Histology and Embryology; School of Medicine; University of Athens; Athens Greece; Faculty Institute of Cancer Sciences; University of Manchester; Manchester Academic Health Science Centre; Manchester UK; Manchester Centre for Cellular Metabolism; University of Manchester; Manchester Academic Health Science Centre; Manchester UK; Biomedical Research Foundation; Academy of Athens; Athens Greece

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Regulation and roles of Cdc7 kinase under replication stress