A quantitative modelling approach for DNA repair on a population scale

by Leo Zeitler, Cyril Denby Wilkes, Arach Goldar, Julie Soutourina

The great advances of sequencing technologies allow the in vivo measurement of nuclear processes—such as DNA repair after UV exposure—over entire cell populations. However, data sets usually contain only a few samples over several hours, missing possibly important information in between time points. We developed a data-driven approach to analyse CPD repair kinetics over time in Saccharomyces cerevisiae. In contrast to other studies that consider sequencing signals as an average behaviour, we understand them as the superposition of signals from independent cells. By motivating repair as a stochastic process, we derive a minimal model for which the parameters can be conveniently estimated. We correlate repair parameters to a variety of genomic features that are assumed to influence repair, including transcription rate and nucleosome density. The clearest link was found for the transcription unit length, which has been unreported for budding yeast to our knowledge. The framework hence allows a comprehensive analysis of nuclear processes on a population scale.