General research interests

DNA lesions arise continuously due to the damaging effects of endogenous or environmental agents. Though living cells are equipped with DNA repair mechanisms, in proliferating cells some of the lesions are inevitably encountered during DNA replication. Stalled replication can lead to incompletely duplicated chromosomes, cell cycle arrest and cell death. Therefore several mechanisms exist that enable the replication machinery to bypass sites of damaged DNA. Successful bypass of lesions allows the cell to survive, but it is the main generator of mutations. Mutagenesis in somatic cells is the main underlying cause of tumorigenesis, and genomic instability is one of the hallmarks of cancer. Our group investigates the mechanisms and consequences of the replication of damaged DNA, and the relevance of mutagenic processes to cancer diagnosis and treatment.

Main research projects

Regulation of DNA damage bypass

At least three distinct mechanisms exist to allow the bypass of lesions by stalled replication forks. Translesion sythesis utilises specialised DNA polymerases to copy the damaged template, and is prone to introducing mutations into the new DNA strand. In contrast, the processes of template switching and homologous recombination both allow the avoidance of the lesion, using the daughter strand of the sister chromatid as an alternative template. We study the mechanisms that govern the choice of bypass pathway, thereby determining the type and frequency of genomic mutations generated by lesion bypass.

Translesion synthesis

We study the roles of participating proteins and covalent protein modifications in the selection of the DNA polymerase and in the temporal regulation of translesion synthesis. In addition, we investigate the dependence of the arising mutations on the type of lesion, the participating DNA polymerase and the regulatory mechanisms.

Modelling mutagenic processes in cancer

We use simplified tumour models based on genetically modified cell lines to investigate the causes and consequences of mutagenesis and genomic instability of tumour cells. We concentrate on the mutagenic consequences of impaired DNA repair, and potential mutagenesis due to chemotherapeutic treatments.

DT40 cell line genetics

Part of our work makes use of knock-out and other mutant cells generated from the DT40 chicken cell line. The DT40 bursal lymphoma line is uniquely amenable to targeted genetic modifications amongst vertebrate cell culture systems. The use of  DT40 cells is well established in the field of DNA repair, and due to the high degree of conservation of most proteins involved in these processes the results are entirely relevant for understanding the equivalent processes in human cells. The rapidly dividing DT40 cells are especially useful for genetic studies of the replication of damaged DNA. We have sequenced and characterised the genome of the DT40 cell line, which is available for downloading or BLAST searches at

Genomic analyses and method development

Next generation DNA sequencing allows the analysis of mutagenesis on the genomic scale. We are using whole genome sequencing to detect the influence of various DNA repair processes on mutagenesis. In collaboration with bioinformatics groups, we are also working to develop accurate methods of mutation detection based on whole genome sequence data.

Main recent publications

Szüts D. (2022). A fresh look at somatic mutations in cancer. Science 376, 351-352.

Chen D, Gervai JZ, Póti Á, Németh E, Szeltner Z, Szikriszt B, Gyüre Z, Zámborszky J, Ceccon M, d’Adda di Fagagna F, Szallasi Z, Richardson AL, Szüts D. (2022). BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1. Nat Commun. 13, 226.

Póti Á, Szikriszt B, Gervai JZ, Chen D, Szüts D. (2022). Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis. PLoS Genet. 18, e1010051.

Szeltner Z, Póti Á, Harami GM, Kovács M, Szüts D. (2021). Evaluation and modulation of DNA lesion bypass in an SV40 large T antigen-based in vitro replication system. FEBS Open Bio. 11, 1054-1075.

Szikriszt B, Póti Á, Németh E, Kanu N, Swanton C, Szüts D. (2021). A comparative analysis of the mutagenicity of platinum-containing chemotherapeutic agents reveals direct and indirect mutagenic mechanisms. Mutagenesis 36, 75-86.

Németh E, Lovrics A, Gervai JZ, Seki M, Rospo G, Bardelli A, Szüts D. (2020). Two main mutational processes operate in the absence of DNA mismatch repair. DNA Repair (Amst). 89, 102827.

Póti Á, Gyergyák H, Németh E, Rusz O, Tóth S, Kovácsházi C, Chen D, Szikriszt B, Spisák S, Takeda S, Szakács G, Szallasi Z, Richardson AL, Szüts D. (2019). Correlation of homologous recombination deficiency induced mutational signatures with sensitivity to PARP inhibitors and cytotoxic agents. Genome Biol. 20, 240.

Németh E, Krzystanek M, Reiniger L, Ribli D, Pipek O, Sztupinszki Z, Glasz T, Csabai I, Moldvay J, Szallasi Z, Szüts D. (2019). The genomic imprint of cancer therapies helps timing the formation of metastases. Int J Cancer 145, 694-704.

Póti Á, Berta K, Xiao Y, Pipek O, Klus GT, Ried T, Csabai I, Wilcoxen K, Mikule K, Szallasi Z, Szüts D. (2018). Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts. Br J Cancer 119, 1392-1400.

Gervai JZ, Gálicza J, Szeltner Z, Zámborszky J, Szüts D. (2017). A genetic study based on PCNA-ubiquitin fusions reveals no requirement for PCNA polyubiquitylation in DNA damage tolerance. DNA Repair (Amst). 54, 46-54.

Zámborszky J, Szikriszt B, Gervai J, Pipek O, Póti Á, Ribli D, Krzystanek M, Szalai-Gindl JM, Swanton C, Szallasi Z, Csabai I, Richardson AL, Szüts D. (2017). Loss of BRCA1 or BRCA2 markedly increases the rate of base substitution mutagenesis and has distinct effects on genomic deletions. Oncogene 36, 746-755.

Szikriszt B, Póti Á, Pipek O, Krzystanek M, Kanu N, Molnár J, Ribli D, Szeltner Z, Tusnády GE, Csabai I, Szállási Z, Swanton C, Szüts D. (2016). A comprehensive curvey of the mutagenic impact of common cancer cytotoxics. Genome Biol. 17, 99.


Group Leader

Dávid Szüts MA PhD