title: Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.
abstract: Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF-ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer.
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.affiliation: College of Pharmacy, University of Illinois, Rockford, Illinois 61107, USA.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Shar-Yin N
authors.initials: SN
authors.lastname: Huang
authors.affiliation: College of Pharmacy, University of Illinois, Rockford, Illinois 61107, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Nitiss
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D026942:DNA Topoisomerases / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D026942:DNA Topoisomerases