Figure 6. Model of SPRTN removal of DNA-protein crosslinks.
DNA-protein crosslinks may arise stochastically as a consequence of normal metabolic processes occurring at or in the vicinity of DNA or by exogenous sources such as Etoposide. DPCs are resolved by SPRTN to allow for unperturbed and timely DNA replication. When SPRTN is absent or when its activity is compromised, such as in patients with Ruijs-Aalfs syndrome (SPRTN-Y117C or SPRTN-∆C), DPCs can persist and perturb DNA replication and transcription (not shown). DPCs, if not resolved, can lead to genomic instability, tumorigenesis and contribute to accelerated aging.