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- W2523410070 endingPage "721" @default.
- W2523410070 startingPage "703" @default.
- W2523410070 abstract "Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, thereby mediating chromatin dynamics and stability, transcription, replication and DNA damage repair. Topoisomerases are targets of various anticancer drugs, and their deregulation can cause, in addition to cancer, neurodegenerative diseases and immune disorders. 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." @default.
- W2523410070 created "2016-09-30" @default.
- W2523410070 creator A5022566853 @default.
- W2523410070 creator A5042114293 @default.
- W2523410070 creator A5047356461 @default.
- W2523410070 creator A5047941791 @default.
- W2523410070 date "2016-09-21" @default.
- W2523410070 modified "2023-10-17" @default.
- W2523410070 title "Roles of eukaryotic topoisomerases in transcription, replication and genomic stability" @default.
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