parkin regulates translesion dna synthesis in response to uv radiation deficiency of parkin is a major cause of earlyonset parkinsons disease pd notably pd patients also exhibit a significantly higher risk in melanoma and other skin tumors while the mechanism remains largely unknown in this study we show that depletion of parkin causes compromised cell viability and genome stability after ultraviolet uv radiation we demonstrate that parkin promotes efficient rad18dependent proliferating cell nuclear antigen pcna monoubiquitination by facilitating the formation of replication protein a rpacoated ssdna upon uv radiation furthermore parkin is found to physically interact with nbs1 nijmegen breakage syndrome 1 and to be required for optimal recruitment of nbs1 and dna polymerase eta pol to uvinduced damage sites consequently depletion of parkin leads to increased uvinduced mutagenesis these findings unveil an important role of parkin in protecting genome stability through positively regulating translesion dna synthesis tls upon uv damage providing a novel mechanistic link between parkin deficiency and predisposition to skin cancers in pd patients