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When exposed to PARPi, SF3B1 MUT cells show an impaired replication stress response (lack of pCHK1 (S317), pATR and pRPA32) due to reduced CINP protein expression. This leads to increased origin firing, unchecked fork progression and unresolved replication intermediates via the lack of MUS81-positive FANCD2 foci. This results in ATM activation and the induction of pCHK2 (T68), stalling SF3B1 MUT cells at the G 2 /M checkpoint.

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