title: The DNA damage checkpoint response to replication stress: A Game of Forks.
abstract: Conditions challenging replication fork progression, collectively referred to as replication stress, represent a major source of genomic instability and are associated to cancer onset. The replication checkpoint, a specialized branch of the DNA damage checkpoint, monitors fork problems, and triggers a cellular response aimed at preserving genome integrity. Here, we review the mechanisms by which the replication checkpoint monitors and responds to replication stress, focusing on the checkpoint-mediated pathways contributing to protect replication fork integrity. We discuss how cells achieve checkpoint signaling inactivation once replication stress is overcome and how a failure to timely revert checkpoint-mediated changes in cellular physiology might impact on replication dynamics and genome integrity. We also highlight the checkpoint function as an anti-cancer barrier preventing cells malignant transformation following oncogene-induced replication stress.
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/USAL Salamanca, Spain.
authors.forename: Rachel
authors.initials: R
authors.lastname: Jossen
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bermejo
keywords: DNA damage checkpoint; Mec1/ATR; genomic instability; oncogene stress; replication forks