School of Mathematics

Sjoerd Beentjes has collaborated with others on a paper; "Pervasive lesion segregation shapes cancer genome evolution"

Sjoerd Beentjes has collaborated with others, from across multiple Universities and Organisations, to produce an article discussing the effects of damage to DNA with regards to the development of cancer cells. This work took place in 2019 with the article being published in June of 2020.

The article, titled 'Pervasive lesion segregation shapes cancer genome evolution', came out of a project investigating how cancers arise through the acquisition of tumour generating mutations and grow via mitosis. This project sought to determine how DNA damage can cause mutations due to failures in DNA repair and errors during DNA replication.

The work was conducted by characterizing the above-mentioned process in mutagen-induced mouse liver tumours, showing that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions. This generates an array of genetic diversity.

Sjoerd contributed by discussing ideas and offering a statistical/mathematical model to estimate how many cell generations lesions are expected to last. This model confirmed, from a mathematical perspective, the hypothesis that lesions in the DNA persist over several cell divisions.

The results showed that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. The initial damage is exacerbated over time as the cells divide.

The full article can be found here: https://www.jdsupra.com/legalnews/genetic-lesion-segregation-found-in-34910/

Further discussed here: https://www.nature.com/articles/d41586-020-01815-6