Polymerase iota plays a key role during translesion synthesis of UV-induced lesions in the absence of polymerase eta

Xeroderma pigmentosum (XP) variant cells are deficient in the translesion synthesis (TLS) DNA polymerase Pol eta (eta). This protein contributes to DNA damage tolerance, bypassing unrepaired UV photoproducts and allowing S-phase progression with minimal delay. In the absence of Pol eta, backup polymerases perform TLS of UV lesions. However, which polymerase plays this role in human cells remains an open question. Here, we investigated the potential role of Pol iota (iota) in bypassing ultraviolet (UV) induced photoproducts in the absence of Pol eta, using NER-deficient (XP-C) cells knocked down for Pol iota and/or Pol eta genes. Our results indicate that cells lacking either Pol iota or Pol eta have increased sensitivity to UVC radiation. The lack of both TLS polymerases led to increased cell death and defects in proliferation and migration. Loss of both polymerases induces a significant replication fork arrest and G1/S-phase blockage, compared to the lack of Pol eta alone. In conclusion, we propose that Pol iota acts as a bona fide backup for Pol eta in the TLS of UV-photoproducts.

Automated summary

Xeroderma pigmentosum (XP) variant cells deficient in Polη polymerase show increased sensitivity to UV radiation, affecting cell proliferation and migration. Polι may act as a backup for Polη in bypassing UV-induced photoproducts.