Fig. 7: Model for G4 DNA-induced second hit mutations in hPKD1.

Somatic cells heterozygous for a pathogenic PKD1 allele (PKD1+/−) do not lead to cysts, left. G4 DNA forms in PKD1 during replication, center. G4 DNAs block DNA metabolism and increases the risk of double strand breaks (DSB) in the remaining normal allele, right. Second hit inactivation (PKD1−/−) due to G4 DNA formation lowers polycystin-1 levels and leads to cell proliferation and cystogenesis. Created in BioRender, Bouma, J. (2024) BioRender.com/v35i306.