{"entity": "researcher", "timestamp": "2026-08-20T21:19:56.943Z", "family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd"}}, "publications": [{"entity": "publication", "iuid": "05055972eaff415c8f51b09d91d400fd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/05055972eaff415c8f51b09d91d400fd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/05055972eaff415c8f51b09d91d400fd"}}, "title": "The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.", "authors": [{"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Bonagas", "given": "Nadilly", "initials": "N"}, {"family": "Chalkiadaki", "given": "Christina", "initials": "C"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Schelzig", "given": "Korbinian", "initials": "K", "orcid": "0009-0001-3791-0716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5ffa105eeea4750a28fd7b1f4b3e4de.json"}}, {"family": "Shen", "given": "Jianyu", "initials": "J"}, {"family": "Farhat", "given": "Crystal M", "initials": "CM"}, {"family": "Hondema", "given": "Amber", "initials": "A"}, {"family": "Albers", "given": "Julian", "initials": "J"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Slipicevic", "given": "Ana", "initials": "A"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2024-09-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "18", "issue": "9", "pages": "2179-2195", "issn-l": "1574-7891"}, "abstract": "The one-carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)- and DNA-dependent protein kinase (DNA-PK)-dependent manner. Furthermore, repair of IR-induced DNA double-strand breaks (DSBs) is delayed upon MTHFD2 knockdown, suggesting a role for MTHFD2 in DSB repair. In support of this, we observe impaired recruitment of replication protein A (RPA), reduced resection, decreased IR-induced DNA repair protein RAD51 homolog 1 (RAD51) levels and impaired homologous recombination (HR) activity in MTHFD2-depleted cells following IR. In conclusion, we identify a key role for MTHFD2 in HR repair and describe an interdependency between MTHFD2 and HR proficiency that could potentially be exploited for cancer therapy.", "doi": "10.1002/1878-0261.13645", "pmid": "38533616", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11467796"}], "notes": [], "created": "2026-08-20T06:26:58.460Z", "modified": "2026-08-20T06:26:58.641Z"}, {"entity": "publication", "iuid": "722ce11b086b44db9af41560e1478a57", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/722ce11b086b44db9af41560e1478a57.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/722ce11b086b44db9af41560e1478a57"}}, "title": "NUDT22 promotes cancer growth through pyrimidine salvage.", "authors": [{"family": "Walter", "given": "Melanie", "initials": "M", "orcid": "0000-0003-3241-522X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d7c13aca7b7474ead126c17d2d87160.json"}}, {"family": "Mayr", "given": "Florian", "initials": "F", "orcid": "0000-0002-0892-7076", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/18f5bceb8fbe4b3f90fb31191a89118b.json"}}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Cookson", "given": "Victoria", "initials": "V"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Herr", "given": "Patrick", "initials": "P", "orcid": "0000-0003-2945-966X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0140001cd2214241af0f5adc955321ae.json"}}], "type": "journal article", "published": "2023-04-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "42", "issue": "16", "pages": "1282-1293", "issn-l": "0950-9232"}, "abstract": "The NUDIX hydrolase NUDT22 converts UDP-glucose into glucose-1-phosphate and the pyrimidine nucleotide uridine monophosphate but a biological significance for this biochemical reaction has not yet been established. Glucose-1-phosphate is an important metabolite for energy and biomass production through glycolysis and nucleotides required for DNA replication are produced through energetically expensive de novo or energy-efficient salvage pathways. Here, we describe p53-regulated pyrimidine salvage through NUDT22-dependent hydrolysis of UDP-glucose to maintain cancer cell growth and to prevent replication stress. NUDT22 expression is consistently elevated in cancer tissues and high NUDT22 expression correlates with worse survival outcomes in patients indicating an increased dependency of cancer cells to NUDT22. Furthermore, we show that NUDT22 transcription is induced after inhibition of glycolysis, MYC-mediated oncogenic stress, and DNA damage directly through p53. NUDT22-deficient cancer cells suffer from growth retardation, S-phase delay, and slower DNA replication fork speed. Uridine supplementation rescues replication fork progression and alleviates replication stress and DNA damage. Conversely, NUDT22 deficiency sensitizes cells to de novo pyrimidine synthesis inhibition in vitro and reduces cancer growth in vivo. In conclusion, NUDT22 maintains pyrimidine supply in cancer cells and depletion of NUDT22 leads to genome instability. Targeting NUDT22 therefore has high potential for therapeutic applications in cancer therapy.", "doi": "10.1038/s41388-023-02643-4", "pmid": "36871087", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10101856"}, {"db": "pii", "key": "10.1038/s41388-023-02643-4"}], "notes": [], "created": "2026-08-20T08:48:33.235Z", "modified": "2026-08-20T08:48:33.467Z"}, {"entity": "publication", "iuid": "ad59b1b98d8c42d881dd45a6ac12c52a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ad59b1b98d8c42d881dd45a6ac12c52a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ad59b1b98d8c42d881dd45a6ac12c52a"}}, "title": "Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48bb9c8ab8a5465a8a4da1997f1af56d.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Alam", "given": "Seher", "initials": "S", "orcid": "0000-0002-8494-832X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38a0280842714f1f92e6b54f49dcb559.json"}}, {"family": "Pires", "given": "Maria J", "initials": "MJ"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Langelier", "given": "Marie France", "initials": "MF", "orcid": "0000-0001-9815-1840", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/79beb7ce9d3b46528f35b1cf9038cf65.json"}}, {"family": "Rehling", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8627-3469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5aff0e51eb124b7183a9e752256288a4.json"}}, {"family": "Throup", "given": "Adam", "initials": "A", "orcid": "0000-0001-6512-8679", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d7373aaa685464492b615ea4152b843.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b251e222615747a7822bf3cc26749cde.json"}}, {"family": "Onireti", "given": "Jacob", "initials": "J"}, {"family": "Wakchaure", "given": "Prasad", "initials": "P", "orcid": "0000-0003-2828-4642", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d20f3f040894567b699c50b8b9e9fd4.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e6b3b2450f0498f9d0be4d9af615e89.json"}}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Benzi", "given": "Giorgia", "initials": "G"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Pascal", "given": "John M", "initials": "JM", "orcid": "0000-0002-2714-4317", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82a900bd9df84da594641911c65750f1.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6cb0faad98c34cf7b9d4f60d03274727.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d77b74fe6e7d44f4800fe8bb4404ad8f.json"}}], "type": "posted-content", "published": "2022-09-19", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.09.19.505646", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:14:18.579Z", "modified": "2026-08-20T10:14:19.029Z"}, {"entity": "publication", "iuid": "5c5bfa7eea964cf7961bdec3453b5d92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92"}}, "title": "Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f4696e361fe4aa3823d263674d1a498.json"}}, {"family": "Ben\u00edtez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Calvo", "given": "Patricia A", "initials": "PA"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c62ba219d3e34662aaa458dbd361cf31.json"}}, {"family": "Davies", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-4986-8594", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e74e0781a72d480c8e705a9a824e5e5a.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3601a5a4d88f4452b6d1ac5f22c79d9f.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Albers", "given": "Julian J", "initials": "JJ", "orcid": "0000-0001-9579-6360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8278cc4e9e7e4bde823f672b1982591d.json"}}, {"family": "Casta\u00f1eda-Zegarra", "given": "Sergio", "initials": "S", "orcid": "0000-0002-2808-6788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3438015dbc1d41b797a02c25a37fef60.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9fef10d6a8604971a6ad1849b9f8b029.json"}}, {"family": "Sastre-Perona", "given": "Ana", "initials": "A", "orcid": "0000-0002-4502-3025", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7d1f1df32dbd449c8f10a5ce0872a6b3.json"}}, {"family": "Danda", "given": "Akhilesh N", "initials": "AN"}, {"family": "Homan", "given": "Evert J", "initials": "EJ", "orcid": "0000-0002-9057-1848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a68aa16414c4c159c52a5e75d5537c1.json"}}, {"family": "Marimuthu", "given": "Karthick", "initials": "K"}, {"family": "Zhenjun", "given": "Zhao", "initials": "Z", "orcid": "0000-0003-1976-0790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/019926f6c3d649ea9b04b7b37956dfda.json"}}, {"family": "Chi", "given": "Celestine N", "initials": "CN"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22883e442f534ba99f2917cf45d95b3d.json"}}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "von Nicolai", "given": "Catharina", "initials": "C", "orcid": "0000-0002-7116-2635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b6a7ea3d84de4bcb9366c5dcb5b36779.json"}}, {"family": "Komor", "given": "Anna J", "initials": "AJ", "orcid": "0000-0003-4806-4233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c3ee8bcb2ee41f1982b48bfed84b76f.json"}}, {"family": "Rajagopal", "given": "Varshni", "initials": "V"}, {"family": "M\u00fcller", "given": "Sarah", "initials": "S", "orcid": "0000-0002-9923-3298", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5012b873ff66448eb2e0ae2e284f7b5b.json"}}, {"family": "Hank", "given": "Emily C", "initials": "EC", "orcid": "0000-0002-3777-4697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b412977f2364bef9ec63aa5e552331a.json"}}, {"family": "Varga", "given": "Marek", "initials": "M", "orcid": "0000-0002-9685-8145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/707532fc225c49d1b2d4f9bec632e13f.json"}}, {"family": "Scaletti", "given": "Emma R", "initials": "ER", "orcid": "0000-0002-8741-8981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Pandey", "given": "Monica", "initials": "M", "orcid": "0000-0002-5783-5995", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d5af32166634f20b29a5f1ed9e12c43.json"}}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "Haslene-Hox", "given": "Hanne", "initials": "H"}, {"family": "Loevenich", "given": "Simon", "initials": "S", "orcid": "0000-0001-5424-8755", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a06b60008414ef09b0c1e360ae1d10f.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Mamonov", "given": "Kirill", "initials": "K", "orcid": "0000-0001-5971-4305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2aeb36f9611f4c03883b8def30565da1.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F", "orcid": "0000-0002-0458-5187", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2e13b716bc349eb9dac083d7f801549.json"}}, {"family": "Sch\u00f6mberg", "given": "Fritz", "initials": "F", "orcid": "0000-0003-0092-0627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f10b06057e94d03a44967cce431c1a8.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Stewart", "given": "Josephine", "initials": "J"}, {"family": "D'Arcy-Evans", "given": "Nicholas", "initials": "N"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Michel", "given": "Dana", "initials": "D"}, {"family": "de Ory", "given": "Ana", "initials": "A"}, {"family": "Acero", "given": "Lucia", "initials": "L", "orcid": "0000-0001-8101-5412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af80832b8d8c4019bea17c15fa7651e2.json"}}, {"family": "Calvete", "given": "Oriol", "initials": "O", "orcid": "0000-0002-2623-2876", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ee0251167344b24b97b971b8c750795.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdce0df415d54e9d84a4fcbb4d1350e5.json"}}, {"family": "Hertweck", "given": "Christian", "initials": "C", "orcid": "0000-0002-0367-337X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b1f3fa37a7d4378b06381c2e68a10cb.json"}}, {"family": "Vilotijevic", "given": "Ivan", "initials": "I", "orcid": "0000-0001-6199-0632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eec3fc0f230046ccbe7ff46b2da70792.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C", "orcid": "0000-0001-7004-7048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9c7121a5e14414b8bace2708e8add2f.json"}}, {"family": "Osorio", "given": "Ana", "initials": "A", "orcid": "0000-0001-8124-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ecd4cc9c17d43009703efb95d979e09.json"}}, {"family": "Perona", "given": "Rosario", "initials": "R", "orcid": "0000-0002-2973-5153", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b116837f5c346d49e70ad5eb28d7afb.json"}}, {"family": "Stolz", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-3340-439X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4bde36f21953479a8762c1c858b4c451.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6196fa790b4645c3acef45a87cdac3d0.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2022-06-24", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "376", "issue": "6600", "pages": "1471-1476", "issn-l": "0036-8075"}, "abstract": "Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed \u03b2,\u03b4-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.", "doi": "10.1126/science.abf8980", "pmid": "35737787", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:29.051Z", "modified": "2026-08-20T11:59:30.134Z"}, {"entity": "publication", "iuid": "772c66fd0f16493a84a86f88ac367a62", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/772c66fd0f16493a84a86f88ac367a62.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/772c66fd0f16493a84a86f88ac367a62"}}, "title": "NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487.", "authors": [{"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f4696e361fe4aa3823d263674d1a498.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}], "type": "journal article", "published": "2021-04-27", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "22", "issue": "9", "issn-l": null}, "abstract": "DNA damage caused by reactive oxygen species may result in genetic mutations or cell death. Base excision repair (BER) is the major pathway that repairs DNA oxidative damage in order to maintain genomic integrity. In mammals, eleven DNA glycosylases have been reported to initiate BER, where each recognizes a few related DNA substrate lesions with some degree of overlapping specificity. 7,8-dihydro-8-oxoguanine (8-oxoG), one of the most abundant DNA oxidative lesions, is recognized and excised mainly by 8-oxoguanine DNA glycosylase 1 (OGG1). Further oxidation of 8-oxoG generates hydantoin lesions, which are recognized by NEIL glycosylases. Here, we demonstrate that NEIL1, and to a lesser extent NEIL2, can potentially function as backup BER enzymes for OGG1 upon pharmacological inhibition or depletion of OGG1. NEIL1 recruitment kinetics and chromatin binding after DNA damage induction increase in cells treated with OGG1 inhibitor TH5487 in a dose-dependent manner, whereas NEIL2 accumulation at DNA damage sites is prolonged following OGG1 inhibition. Furthermore, depletion of OGG1 results in increased retention of NEIL1 and NEIL2 at damaged chromatin. Importantly, oxidatively stressed NEIL1- or NEIL2-depleted cells show excessive genomic 8-oxoG lesions accumulation upon OGG1 inhibition, suggesting a prospective compensatory role for NEIL1 and NEIL2. Our study thus exemplifies possible backup mechanisms within the base excision repair pathway.", "doi": "10.3390/ijms22094542", "pmid": "33925271", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8123590"}, {"db": "pii", "key": "ijms22094542"}], "notes": [], "created": "2026-08-20T13:41:20.078Z", "modified": "2026-08-20T13:41:20.130Z"}, {"entity": "publication", "iuid": "6315feb800e343aeb5d3716434ad0e92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6315feb800e343aeb5d3716434ad0e92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6315feb800e343aeb5d3716434ad0e92"}}, "title": "MTH1 Inhibitor TH588 Disturbs Mitotic Progression and Induces Mitosis-Dependent Accumulation of Genomic 8-oxodG.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Amaral", "given": "Nuno", "initials": "N"}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Groth", "given": "Petra", "initials": "P"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "17", "pages": "3530-3541", "issn-l": "0008-5472"}, "abstract": "Reactive oxygen species (ROS) oxidize nucleotide triphosphate pools (e.g., 8-oxodGTP), which may kill cells if incorporated into DNA. Whether cancers avoid poisoning from oxidized nucleotides by preventing incorporation via the oxidized purine diphosphatase MTH1 remains under debate. Also, little is known about DNA polymerases incorporating oxidized nucleotides in cells or how oxidized nucleotides in DNA become toxic. Here we show that replacement of one of the main DNA replicases in human cells, DNA polymerase delta (Pol \u03b4), with an error-prone variant allows increased 8-oxodG accumulation into DNA following treatment with TH588, a dual MTH1 inhibitor and microtubule targeting agent. The resulting elevated genomic 8-oxodG correlated with increased cytotoxicity of TH588. Interestingly, no substantial perturbation of replication fork progression was observed, but rather mitotic progression was impaired and mitotic DNA synthesis triggered. Reducing mitotic arrest by reversin treatment prevented accumulation of genomic 8-oxodG and reduced cytotoxicity of TH588, in line with the notion that mitotic arrest is required for ROS buildup and oxidation of the nucleotide pool. Furthermore, delayed mitosis and increased mitotic cell death was observed following TH588 treatment in cells expressing the error-prone but not wild-type Pol \u03b4 variant, which is not observed following treatments with antimitotic agents. Collectively, these results link accumulation of genomic oxidized nucleotides with disturbed mitotic progression. SIGNIFICANCE: These findings uncover a novel link between accumulation of genomic 8-oxodG and perturbed mitotic progression in cancer cells, which can be exploited therapeutically using MTH1 inhibitors.See related commentary by Alnajjar and Sweasy, p. 3459.", "doi": "10.1158/0008-5472.CAN-19-0883", "pmid": "32312836", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-0883"}], "notes": [], "created": "2026-08-20T12:10:55.392Z", "modified": "2026-08-20T12:10:55.497Z"}]}