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

Author(s)

Martins, Davi Jardim ; Singh, Jenny Kaur ; Jahjah, Tiya ; Vessoni, Alexandre Teixeira ; Leandro, Giovana da Silva ; Silva, Matheus Molina ; Biard, Denis Serge Francois ; Quinet, Annabel ; Menck, Carlos Frederico Martins

• Document type: Journal article
• Source: Photochemistry and Photobiology; v. 100, n. 1, p. 15-pg., 2023-11-05.

Abstract

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. (AU)

• FAPESP's process: 17/05680-0 - Mechanisms of translesion synthesis in human cells
• Grantee: Davi Jardim Martins
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants