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This leads to aberrant DNA replication, which triggers a DNA damage response (DDR) involving activation of ATM, Chk1 and Chk2 kinases, and p53, and induction of senescence or apoptosis ( The high frequency of missense TP53 mutations in human tumors and the fact that mutant p53 often accumulates at high levels in tumor cells make mutant p53 a potential target for improved cancer therapy

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When there is a deficit of HGF, neural crest cells fail to migrate sufficiently into the strial intermediate cell layer