{"entity": "researcher", "timestamp": "2026-08-20T20:49:39.897Z", "family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, S-171 76 Stockholm, Sweden annsofie.jemth@scilifelab.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a"}}, "publications": [{"entity": "publication", "iuid": "b28fc4cc0e8a4eaca57d651057592f0b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b28fc4cc0e8a4eaca57d651057592f0b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b28fc4cc0e8a4eaca57d651057592f0b"}}, "title": "Kinetic and structural characterization of NUDT15 and NUDT18 as catalysts of isoprene pyrophosphate hydrolysis.", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Unterlass", "given": "Judith E", "initials": "JE"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Kapsitidou", "given": "Despina", "initials": "D"}, {"family": "Tsuber", "given": "Viktoriia", "initials": "V"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "FEBS J.", "issn": "1742-4658", "volume": "291", "issue": "19", "pages": "4301-4322", "issn-l": "1742-464X"}, "abstract": "Isoprene pyrophosphates play a crucial role in the synthesis of a diverse array of essential nonsterol and sterol biomolecules and serve as substrates for posttranslational isoprenylation of proteins, enabling specific anchoring to cellular membranes. Hydrolysis of isoprene pyrophosphates would be a means to modulate their levels, downstream products, and protein isoprenylation. While NUDIX hydrolases from plants have been described to catalyze the hydrolysis of isoprene pyrophosphates, homologous enzymes with this function in animals have not yet been reported. In this study, we screened an extensive panel of human NUDIX hydrolases for activity in hydrolyzing isoprene pyrophosphates. We found that human nucleotide triphosphate diphosphatase NUDT15 and 8-oxo-dGDP phosphatase NUDT18 efficiently catalyze the hydrolysis of several physiologically relevant isoprene pyrophosphates. Notably, we demonstrate that geranyl pyrophosphate is an excellent substrate for NUDT18, with a catalytic efficiency of 2.1 \u00d7 105 m-1\u00b7s-1, thus making it the best substrate identified for NUDT18 to date. Similarly, geranyl pyrophosphate proved to be the best isoprene pyrophosphate substrate for NUDT15, with a catalytic efficiency of 4.0 \u00d7 104 M-1\u00b7s-1. LC-MS analysis of NUDT15 and NUDT18 catalyzed isoprene pyrophosphate hydrolysis revealed the generation of the corresponding monophosphates and inorganic phosphate. Furthermore, we solved the crystal structure of NUDT15 in complex with the hydrolysis product geranyl phosphate at a resolution of 1.70 \u00c5. This structure revealed that the active site nicely accommodates the hydrophobic isoprenoid moiety and helped identify key binding residues. Our findings imply that isoprene pyrophosphates are endogenous substrates of NUDT15 and NUDT18, suggesting they are involved in animal isoprene pyrophosphate metabolism.", "doi": "10.1111/febs.17202", "pmid": "38944687", "labels": [], "xrefs": [{"db": "RefSeq", "key": "XP_003984764.1"}], "notes": [], "created": "2026-08-20T11:18:05.835Z", "modified": "2026-08-20T11:18:05.916Z"}, {"entity": "publication", "iuid": "77475c1df233406b93598c917df16eeb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/77475c1df233406b93598c917df16eeb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/77475c1df233406b93598c917df16eeb"}}, "title": "Kinetic and structural characterization of human NUDIX hydrolases NUDT15 and NUDT18 as catalysts of isoprene pyrophosphate hydrolysis", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER", "orcid": "0000-0002-8741-8981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Unterlass", "given": "Judith E", "initials": "JE", "orcid": "0000-0002-7504-8338", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0aa7804a71ab4293aca5a78554737016.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Kapsitidou", "given": "Despina", "initials": "D"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "posted-content", "published": "2023-11-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2023.11.29.569174", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:50:34.757Z", "modified": "2026-08-20T10:50:34.875Z"}, {"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": "85dfc86719fd4e699a0a07008f7b0f67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67"}}, "title": "Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.", "authors": [{"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2981680ce6de48ca84cfee5f74a94f27.json"}}, {"family": "Unterlass", "given": "Judith", "initials": "J"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal article", "published": "2020-08-14", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "295", "issue": "33", "pages": "11656-11668", "issn-l": "0021-9258"}, "abstract": "The bifunctional human enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) catalyzes two essential steps in the de novo purine biosynthesis pathway. PAICS is overexpressed in many cancers and could be a promising target for the development of cancer therapeutics. Here, using gene knockdowns and clonogenic survival and cell viability assays, we demonstrate that PAICS is required for growth and survival of prostate cancer cells. PAICS catalyzes the carboxylation of aminoimidazole ribonucleotide (AIR) and the subsequent conversion of carboxyaminoimidazole ribonucleotide (CAIR) and l-aspartate to N-succinylcarboxamide-5-aminoimidazole ribonucleotide (SAICAR). Of note, we present the first structures of human octameric PAICS in complexes with native ligands. In particular, we report the structure of PAICS with CAIR bound in the active sites of both domains and SAICAR bound in one of the SAICAR synthetase domains. Moreover, we report the PAICS structure with SAICAR and an ATP analog occupying the SAICAR synthetase active site. These structures provide insight into substrate and product binding and the architecture of the active sites, disclosing important structural information for rational design of PAICS inhibitors as potential anticancer drugs.", "doi": "10.1074/jbc.RA120.013695", "pmid": "32571877", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7450103"}, {"db": "pii", "key": "S0021-9258(17)48465-1"}, {"db": "PDB", "key": "5clj"}, {"db": "PDB", "key": "2h31"}, {"db": "PDB", "key": "4ja0"}, {"db": "PDB", "key": "3rgg"}, {"db": "PDB", "key": "2nsl"}, {"db": "PDB", "key": "2gqs"}, {"db": "PDB", "key": "4fe2"}, {"db": "PDB", "key": "4o7w"}, {"db": "PDB", "key": "2z02"}, {"db": "PDB", "key": "2cnv"}, {"db": "PDB", "key": "2cnu"}, {"db": "PDB", "key": "1obd"}], "notes": [], "created": "2026-08-20T09:32:23.628Z", "modified": "2026-08-20T09:32:23.752Z"}, {"entity": "publication", "iuid": "e8c5934c61524c688421a2e4b3dd5c20", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e8c5934c61524c688421a2e4b3dd5c20.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e8c5934c61524c688421a2e4b3dd5c20"}}, "title": "MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.", "authors": [{"family": "Scaletti", "given": "Emma Rose", "initials": "ER"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22883e442f534ba99f2917cf45d95b3d.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "journal article", "published": "2020-04-10", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "295", "issue": "15", "pages": "4761-4772", "issn-l": "0021-9258"}, "abstract": "MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMP-bound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site subpocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminase-like protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1-catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway.", "doi": "10.1074/jbc.RA120.012636", "pmid": "32144205", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7152754"}, {"db": "pii", "key": "S0021-9258(17)48573-5"}, {"db": "PDB", "key": "3ZR1"}, {"db": "PDB", "key": "3ZR0"}, {"db": "PDB", "key": "5OTM"}, {"db": "PDB", "key": "6QVO"}, {"db": "PDB", "key": "5OTN"}, {"db": "PDB", "key": "6FL4"}, {"db": "PDB", "key": "3A6T"}], "notes": [], "created": "2026-08-20T09:32:21.804Z", "modified": "2026-08-20T09:32:21.945Z"}, {"entity": "publication", "iuid": "565c8ebd51d44e2ebe08d32f106f0c85", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/565c8ebd51d44e2ebe08d32f106f0c85.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/565c8ebd51d44e2ebe08d32f106f0c85"}}, "title": "MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells", "authors": [{"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Stolz", "given": "Ailine", "initials": "A", "orcid": "0000-0002-1051-7527", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd53f689f44b4e8b928ebe2e77f41999.json"}}, {"family": "Amaral", "given": "Nuno", "initials": "N"}, {"family": "Brautigham", "given": "Lars", "initials": "L"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Kald\u00e9ren", "given": "Christina", "initials": "C"}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Visnes", "given": "Torkild", "initials": "T"}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Calderon Montano", "given": "Jos\u00e9 Manuel", "initials": "JM"}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Groth", "given": "Petra", "initials": "P"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Gokturk", "given": "Camilla", "initials": "C"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Wakchaure", "given": "Prasad", "initials": "P"}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Bastians", "given": "Holger", "initials": "H"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "posted-content", "published": "2019-03-12", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/575290", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:10.066Z", "modified": "2026-08-20T11:13:10.124Z"}]}