title: DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: Cell cycle and proliferation-dependent regulation.
abstract: Eukaryotic cells respond to DNA damage by activating a comprehensive network of biochemical pathways that enable damage recognition and initiate responses leading to repair, apoptosis/autophagy or senescence. This network of responses is commonly described as the "DNA damage response" (DDR). Among the plethora of lesions generated in the DNA from various physical and chemical agents in the environment and in the cell, DNA double strand breaks (DSBs) and DNA replication stress (RS) are the most severe and induce strong DDR, as they bear high risk for cell death, or genomic alterations ultimately causing cancer. Here, we focus on DSBs and provide a state-of-the-art review of the molecular underpinnings of repair pathways that process DSBs in higher eukaryotes, their strengths and limitations, as well as aspects of repair pathway choice and hierarchy. Furthermore, we discuss the regulation of DSB repair pathways throughout the cell cycle and by processes affecting the proliferative state of the cell. We review the role of growth factors and their receptors in the regulation of each DSB repair pathway and discuss aspects of systemic regulation of DNA repair.
authors.affiliation: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, 45122 Essen, Germany.
authors.forename: Emil
authors.initials: E
authors.lastname: Mladenov
authors.affiliation: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, 45122 Essen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Magin
authors.affiliation: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, 45122 Essen, Germany.
authors.forename: Aashish
authors.initials: A
authors.lastname: Soni
authors.affiliation: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, 45122 Essen, Germany. Electronic address: Georg.Iliakis@uk-essen.de.
authors.forename: George
authors.initials: G
authors.lastname: Iliakis
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D059767:Recombinational DNA Repair
keywords: Cell cycle regulation; Cell growth regulation; DNA end resection; Double strand break repair; HRR; Pathway choice; SSA; alt-EJ; c-NHEJ