Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.

ABSTRACT: Proliferating cells regularly experience replication stress caused by spontaneous DNA damage that results from endogenous reactive oxygen species (ROS), DNA sequences that can assume secondary and tertiary structures, and collisions between opposing transcription and replication machineries. Cancer cells face additional replication stress, including oncogenic stress that results from the dysregulation of fork progression and origin firing, and from DNA damage induced by radiotherapy and most cancer chemotherapeutic agents. Cells respond to such stress by activating a complex network of sensor, signaling and effector pathways that protect genome integrity. These responses include slowing or stopping active replication forks, protecting stalled replication forks from collapse, preventing lat

SUBMITTER: Nickoloff JA 

PROVIDER: S-EPMC9330692 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature