• DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers. D Mas-Ponte, F Supek (2020) Nature Genetics.

We classified patterns of clustered mutagenesis in tumor genomes, identifying a new pattern: nonrecurrent, diffuse hypermutation (omikli). // This mechanism occurs independently of the known focal hypermutation (kataegis), and is associated with DNA repair activity which can provide the single-stranded DNA substrate needed by APOBEC3A enzyme.

• Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes. F Supek, B Lehner (2017) Cell.

Mutation clusters in cancer genomes provide fingerprints of mutagenic mechanisms // Error-free mismatch repair lowers the mutation rate in H3K36me3-marked active genes // Error-prone repair using POLH also targets H3K36me3, contributing driver mutations // UV and alcohol increase error-prone repair, targeting mutations toward active genes.

• Differential DNA mismatch repair underlies mutation rate variation across the human genome. F Supek, B Lehner (2015) Nature.

Somatic mutation rates exhibit tissue-specificity coupled to regional changes in DNA replication timing and gene expression. A temporal deconvolution of mutational signatures in microsatellite-instable tumors of the colon, stomach and uterus demonstrates that post-replicative MMR is the cause of the megabase-scale mutation rate variability in the human genome.

• Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours. A Avgustinova*, A Symeonidi [...] F Supek*, S Aznar-Benitah* (2018) Nature Cell Biology. (*corresponding authors)

Loss of activity of a H3K9 methyltransferase doesn't alter the global landscape of mutations in chemically induced tumors // DNA replication time and H3K36me3 histone mark, not chromatin accesibility, are determinants of mutation rates // H3K9me2/3-depleted tumors are genomically instable, and after a prolonged latency, very agressive