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The regulation of gene expression is associated with topoisomerase activity that regulates chromosome topology, movement, and DNA torsional stress during transcription initiation and elongation. Abortive intermediates of TOP1 or TOP2 activity can arise during these processes, creating SSBs (TOP1/TOP2) or DSBs (TOP2) that further impede transcription and threaten genome integrity and stability. Similarly, elevated cytosine deamination in single-stranded DNA during transcription elongation, or programmed BER reactions employed to demethylate cytosine during epigenetic (re)programming and gene activation, can lead to persistent DNA strand breaks and/or potentially mutagenic intermediates if BER is not completed rapidly or accurately.
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