The remarkable stability of the human genome is lost in cancer cells due to the failure of efficient and accurate DNA repair in the context of oncogene-induced replication stress and elevated transcription. Intertwined roles of repair with replication and transcription are emerging for dynamic complexes acting in genome stability and its loss in cancer. Moreover, the synthetic lethality and essentiality resulting from replication-repair stresses suggest strategies to define and predict pathway selection and damage outcomes as a foundation for advanced…

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