title: Topoisomerase-mediated chromosomal break repair: an emerging player in many games.
abstract: The mammalian genome is constantly challenged by exogenous and endogenous threats. Although much is known about the mechanisms that maintain DNA and RNA integrity, we know surprisingly little about the mechanisms that underpin the pathology and tissue specificity of many disorders caused by defective responses to DNA or RNA damage. Of the different types of endogenous damage, protein-linked DNA breaks (PDBs) are emerging as an important player in cancer development and therapy. PDBs can arise during the abortive activity of DNA topoisomerases, a class of enzymes that modulate DNA topology during several chromosomal transactions, such as gene transcription and DNA replication, recombination and repair. In this Review, we discuss the mechanisms underpinning topoisomerase-induced PDB formation and repair with a focus on their role during gene transcription and the development of tissue-specific cancers.
authors.affiliation: 1] Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK. [2] Center for Genomics, Helmy Institute, Zewail City of Science and Technology, Giza 12588, Egypt.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Ashour
authors.affiliation: Center for Genomics, Helmy Institute, Zewail City of Science and Technology, Giza 12588, Egypt.
authors.forename: Reham
authors.initials: R
authors.lastname: Atteya
authors.affiliation: 1] Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK. [2] Center for Genomics, Helmy Institute, Zewail City of Science and Technology, Giza 12588, Egypt.
authors.forename: Sherif F
authors.initials: SF
authors.lastname: El-Khamisy
mesh_terms: D063646:Carcinogenesis; D019457:Chromosome Breakage; D053960:DNA Breaks; D004260:DNA Repair; D026942:DNA Topoisomerases / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D026942:DNA Topoisomerases