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This protein contributes to DNA damage tolerance, bypassing unrepaired UV photoproducts and allowing S\u2010phase progression with minimal delay. In the absence of Pol\u03b7, 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\u03b9 (iota) in bypassing ultraviolet (UV) induced photoproducts in the absence of Pol\u03b7, using NER\u2010deficient (XP\u2010C) cells knocked down for Pol\u03b9 and\/or Pol\u03b7 genes. Our results indicate that cells lacking either Pol\u03b9 or Pol\u03b7 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\u2010phase blockage, compared to the lack of Pol\u03b7 alone. In conclusion, we propose that Pol\u03b9 acts as a bona fide backup for Pol\u03b7 in the TLS of UV\u2010photoproducts.<\/jats:p>","DOI":"10.1111\/php.13879","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:38:51Z","timestamp":1699231131000},"page":"4-18","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polymerase iota plays a key role during translesion synthesis of\n                    <scp>UV<\/scp>\n                    \u2010induced lesions in the absence of polymerase eta"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-5162","authenticated-orcid":false,"given":"Davi Jardim","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of S\u00e3o Paulo  Sao Paulo 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Inserm, CEA, Stabilit\u00e9 G\u00e9n\u00e9tique Cellules Souches et Radiations, LRS\/iRCM\/IBFJ  Fontenay\u2010aux\u2010Roses France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Teixeira","family":"Vessoni","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of S\u00e3o Paulo  Sao Paulo Brazil"},{"name":"Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovana da Silva","family":"Leandro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of S\u00e3o Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Molina","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of S\u00e3o Paulo  Sao Paulo 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