title: DNA replication stress: from molecular mechanisms to human disease.
abstract: The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.
authors.affiliation: DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029, Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029, Madrid, Spain. jmendez@cnio.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Méndez
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002453:Cell Cycle; D004260:DNA Repair; D004261:DNA Replication; D004198:Disease Susceptibility; D042822:Genomic Instability; D006801:Humans; D018741:Replication Origin; D013312:Stress, Physiological
keywords: Checkpoint; DNA repair; DNA replication; Replication fork; Replication origin; Replicative stress