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All six factors are highly conserved across diverse organisms spanning yeast to humans, yet no identifiable homolog of the XPA gene exists in many eukaryotes including green plants. Nevertheless, excision repair is reported to be robust in the XPA-lacking organism, Arabidopsis thaliana, which raises a fundamental question of whether excision repair could occur without XPA in other organisms. Here, we performed a phylogenetic analysis of XPA across all species with annotated genomes and then quantitatively measured excision repair in the absence of XPA using the sensitive whole-genome qXR-Seq method in human cell lines and two model organisms, Caenorhabditis elegans and Drosophila melanogaster. We find that although the absence of XPA results in inefficient excision repair and UV-sensitivity in humans, flies, and worms, excision repair of UV-induced DNA damage is detectable over background. These studies have yielded a significant discovery regarding the evolution of XPA protein and its mechanistic role in nucleotide excision repair.<\/jats:p>","DOI":"10.1093\/nar\/gkad1104","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T16:42:23Z","timestamp":1700757743000},"page":"677-689","source":"Crossref","is-referenced-by-count":7,"title":["Cross-species investigation into the requirement of XPA for nucleotide excision repair"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2024-3566","authenticated-orcid":false,"given":"Cansu","family":"Kose","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-5554","authenticated-orcid":false,"given":"Xuemei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4330-3450","authenticated-orcid":false,"given":"Evan B","family":"Dewey","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Chapel Hill , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5642-0712","authenticated-orcid":false,"given":"Mustafa","family":"Malko\u00e7","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Natural Sciences, Sabanci University , Istanbul , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-4070","authenticated-orcid":false,"given":"Og\u00fcn","family":"Adebali","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Natural Sciences, Sabanci University , Istanbul , T\u00fcrkiye"},{"name":"Department of Computational Science-Biological Sciences, T\u00dcBITAK Research Institute for Fundamental Sciences , Gebze , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-677X","authenticated-orcid":false,"given":"Jeff","family":"Sekelsky","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Chapel Hill , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-8194","authenticated-orcid":false,"given":"Laura A","family":"Lindsey-Boltz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-4900","authenticated-orcid":false,"given":"Aziz","family":"Sancar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of North Carolina School of Medicine , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"2024012516132500100_B1","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/218652a0","article-title":"Defective repair replication of DNA in xeroderma pigmentosum","volume":"218","author":"Cleaver","year":"1968","journal-title":"Nature"},{"key":"2024012516132500100_B2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.ge.09.120175.000315","article-title":"Xeroderma pigmentosum: biochemical and genetic characteristics","volume":"9","author":"Cleaver","year":"1975","journal-title":"Annu. 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