Abstract

Stochastic fluctuations in gene expression (‘noise’) are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither). We show here that DNA base-excision repair amplifies transcriptional noise to facilitate cellular reprogramming. Specifically, the DNA-repair protein Apex1, which recognizes both naturally occurring and unnatural base modifications, amplifies expression noise while homeostatically maintaining mean-expression levels. This amplified expression noise originates from shorter duration, higher intensity, transcriptional bursts generated by Apex1-mediated DNA supercoiling.

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