DNA Replication Arrest in Response to Genotoxic Stress Provokes Early Activation of Stress-Activated Protein Kinases (SAPK/JNK)

The stress-activated protein kinases p38α/β and JNK1/2 cooperate with Chk1 to inhibit mitotic entry upon DNA replication arrest

“…Recently, in addition to p38 MAPKs, JNK kinases have also been involved in cell cycle arrest induced by either genotoxic or non-genotoxic insults. [22][23][24][25] In agreement with these reports, we showed that JNK1/2 depletion leads to an impaired cell cycle arrest in response to replication block when Chk1 is inactivated.…”

“…JNK kinase has been recently reported to phosphorylate and inhibit Cdc25 phosphatases, thereby restraining cell cycle progression and preventing mitotic entry under different stress conditions. [22][23][24][25] As shown in Figure 6A, HU and aphidicolin treatments led to JNK1/2 phosphorylation. Activation of JNK1/2 after HU addition was confirmed by the detection of c-Jun phosphorylation, one of its main substrates (Fig.…”

“…Consequently, this kinase has been implicated in the control of mitotic entry in response to various genotoxic and nongenotoxic stress stimuli. [22][23][24][25] Interestingly, Chk1, MK2 and JNK also control the G 2 /M transition in a normal cell cycle. [26][27][28][29] Using asynchronously growing fibroblasts, we previously showed that p38 MAPK promotes cell cycle arrest when DNA replication is blocked, even in cells where Chk1 was inhibited or depleted.…”

Late Activation of Stress-activated Protein Kinases/c-Jun N-terminal Kinases Triggered by Cisplatin-induced DNA Damage in Repair-defective Cells

“…Regarding SAPK/JNK, pharmacological inhibition of replicative DNA polymerase was found to be sufficient for stimulating its dual phosphorylation (73). Bearing this in mind, we speculated that replication-associated events, together with DSBs generated in the absence of TC-NER, might provide the ultimate signal leading to SAPK/JNK activation after long lasting cisplatin treatment.…”

“…Apparently, individual repair factors are required to different extents for late signaling to SAPK/JNK following cisplatin treatment. Of note, XPC protein has also been reported to be essential for SAPK/JNK activation after exposure to UV light (20,73). Collectively, it appears that individual DNA repair proteins have repair-independent crucial functions in the DNA damage response.…”