Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence

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Genome instability is not evenly distributed, but rather is highly elevated at certain genomic loci containing DNA sequences that can fold into non-canonical secondary structures. The four-stranded G-quadruplex or G4 DNA is one such DNA structure capable of instigating transcription and/or replication obstruction and subsequent genome instability. In this study, we used a reporter system to quantitatively measure the level of genome instability occurring at a G4 DNA motif integrated into the yeast genome. We showed that the disruption of Topoisomerase I function significantly elevated various types of genome instability at the highly transcribed G4 motif generating loss of heterozygosity and copy number alterations (deletions and duplications), both of which are frequently observed in cancer genomes.

Vyšlo v časopise: Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004839
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004839

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