{"entity": "researcher", "timestamp": "2026-08-14T12:27:35.741Z", "family": "Espinoza", "given": "Jaime A", "initials": "JA", "orcid": "0000-0002-0731-2715", "affiliations": ["Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8"}}, "publications": [{"entity": "publication", "iuid": "ab9b4fd3312a411fa7600da6cc9fc651", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab9b4fd3312a411fa7600da6cc9fc651.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab9b4fd3312a411fa7600da6cc9fc651"}}, "title": "Precise mapping of single-stranded DNA breaks by sequence-templated erroneous DNA polymerase end-labelling.", "authors": [{"family": "Wenson", "given": "Leonie", "initials": "L", "orcid": "0000-0002-1864-1258", "researcher": {"href": "https://publications.scilifelab.se/researcher/989e0534adbd426386cec5526c5e9668.json"}}, {"family": "Heldin", "given": "Johan", "initials": "J", "orcid": "0000-0002-0915-5303", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8a546798d014cd3a44537ae5db9f889.json"}}, {"family": "Martin", "given": "Marcel", "initials": "M", "orcid": "0000-0002-0680-200X", "researcher": {"href": "https://publications.scilifelab.se/researcher/132afd4fea2e4e86bdf43708c8f49907.json"}}, {"family": "Erbilgin", "given": "Y\u00fccel", "initials": "Y"}, {"family": "Salman", "given": "Bar\u0131\u015f", "initials": "B", "orcid": "0000-0002-7657-8576", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb919f7fcc794c8898fe800056d42f38.json"}}, {"family": "Sundqvist", "given": "Anders", "initials": "A"}, {"family": "Schaal", "given": "Wesley", "initials": "W", "orcid": "0000-0001-6770-0878", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab184845a24f4effb22ec2b338ab8960.json"}}, {"family": "Sandbaumh\u00fcter", "given": "Friederike A", "initials": "FA"}, {"family": "Jansson", "given": "Erik T", "initials": "ET"}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef7ddc09e57745909175e41ac2d1b647.json"}}, {"family": "Davidsson", "given": "Anton", "initials": "A"}, {"family": "Stenerl\u00f6w", "given": "Bo", "initials": "B", "orcid": "0000-0001-8878-8071", "researcher": {"href": "https://publications.scilifelab.se/researcher/22437ff9315d43089232926973feb0d2.json"}}, {"family": "Espinoza", "given": "Jaime A", "initials": "JA", "orcid": "0000-0002-0731-2715", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael", "initials": "M", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Lennartsson", "given": "Johan", "initials": "J"}, {"family": "Spjuth", "given": "Ola", "initials": "O", "orcid": "0000-0002-8083-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/605dbd52684d4e54ae4150a9933abe6e.json"}}, {"family": "S\u00f6derberg", "given": "Ola", "initials": "O", "orcid": "0000-0003-2883-1925", "researcher": {"href": "https://publications.scilifelab.se/researcher/68df823efa304c0b9962684ac1515808.json"}}], "type": "journal article", "published": "2025-08-04", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "16", "issue": "1", "pages": "7130"}, "abstract": "The ability to analyze whether DNA contains lesions is essential in identifying mutagenic substances. Currently, the detection of single-stranded DNA breaks (SSBs) lacks precision. To address this limitation, we develop a method for sequence-templated erroneous end-labelling sequencing (STEEL-seq), which enables the mapping of SSBs. The method requires a highly error-prone DNA polymerase, so we engineer a chimeric DNA polymerase, Sloppymerase, capable of replicating DNA in the absence of one nucleotide. Following the omission of a specific nucleotide (e.g., dATP) from the reaction mixture, Sloppymerase introduces mismatches directly downstream of SSBs at positions where deoxyadenosine should occur. This mismatch pattern, coupled with the retention of sequence information flanking these sites, ensures that the identified hits are bona fide SSBs. STEEL-seq is compatible with a variety of sequencing technologies, as demonstrated using Sanger, Illumina, PacBio, and Nanopore systems. Using STEEL-seq, we determine the SSB/base pair frequency in the human genome to range between 0.7 and 3.8 \u00d7 10-6 with an enrichment in active promoter regions.", "doi": "10.1038/s41467-025-62512-4", "pmid": "40759655", "labels": {"NGI Short read": "Service", "National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12322144"}, {"db": "pii", "key": "10.1038/s41467-025-62512-4"}], "notes": [], "created": "2025-08-19T13:16:23.958Z", "modified": "2025-11-28T10:45:45.544Z"}, {"entity": "publication", "iuid": "f18d7672bbbb4e5dbcd524fde4fbc995", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f18d7672bbbb4e5dbcd524fde4fbc995.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f18d7672bbbb4e5dbcd524fde4fbc995"}}, "title": "The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output.", "authors": [{"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Espinoza", "given": "Jaime A", "initials": "JA", "orcid": "0000-0002-0731-2715", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8.json"}}, {"family": "Zisi", "given": "Asimina", "initials": "A", "orcid": "0000-0002-4253-0275", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cf82380ca6e4cd1985bc9dd23789539.json"}}, {"family": "Sakkas", "given": "Elpidoforos", "initials": "E"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Katsori", "given": "Anna-Maria", "initials": "AM", "orcid": "0000-0002-5975-2931", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a338e7f888b4e7fa663fdd87d667713.json"}}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af59464d2c74c27af7a43fb5d1a670e.json"}}, {"family": "Dyrskj\u00f8t", "given": "Lars", "initials": "L"}, {"family": "Broholm", "given": "Helle", "initials": "H", "orcid": "0000-0002-6029-822X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6d1ef8a71f24d1694aee57b47c22198.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Els\u00e4sser", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-8724-4849", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcf26e35e037499aa1441a7738ba61af.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0d4d98261f41268c76dd91345a1857.json"}}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "32", "issn-l": "2375-2548"}, "abstract": "Eukaryotic initiation factor 4A-III (eIF4A3), a core helicase component of the exon junction complex, is essential for splicing, mRNA trafficking, and nonsense-mediated decay processes emerging as targets in cancer therapy. Here, we unravel eIF4A3's tumor-promoting function by demonstrating its role in ribosome biogenesis (RiBi) and p53 (de)regulation. Mechanistically, eIF4A3 resides in nucleoli within the small subunit processome and regulates rRNA processing via R-loop clearance. EIF4A3 depletion induces cell cycle arrest through impaired RiBi checkpoint-mediated p53 induction and reprogrammed translation of cell cycle regulators. Multilevel omics analysis following eIF4A3 depletion pinpoints pathways of cell death regulation and translation of alternative mouse double minute homolog 2 (MDM2) transcript isoforms that control p53. EIF4A3 expression and subnuclear localization among clinical cancer specimens correlate with the RiBi status rendering eIF4A3 an exploitable vulnerability in high-RiBi tumors. We propose a concept of eIF4A3's unexpected role in RiBi, with implications for cancer pathogenesis and treatment.", "doi": "10.1126/sciadv.abf7561", "pmid": "34348895", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "7/32/eabf7561"}, {"db": "pmc", "key": "PMC8336962"}], "notes": [], "created": "2021-10-01T09:03:24.915Z", "modified": "2023-06-19T11:42:22.695Z"}, {"entity": "publication", "iuid": "2629beeaf3fe4217aa50a38e5732a8f6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2629beeaf3fe4217aa50a38e5732a8f6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2629beeaf3fe4217aa50a38e5732a8f6"}}, "title": "The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity.", "authors": [{"family": "Espinoza", "given": "Jaime A", "initials": "JA", "orcid": "0000-0002-0731-2715", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8.json"}}, {"family": "Zisi", "given": "Asimina", "initials": "A", "orcid": "0000-0002-4253-0275", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cf82380ca6e4cd1985bc9dd23789539.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Watanabe", "given": "Kenji", "initials": "K"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2020-02-00", "journal": {"volume": "27", "issn": "1476-5403", "issue": "2", "pages": "773-789", "title": "Cell Death Differ.", "issn-l": "1350-9047"}, "abstract": "Pharmacological inhibition of ribosome biogenesis is a promising avenue for cancer therapy. Herein, we report a novel activity of the FDA-approved antimalarial drug amodiaquine which inhibits rRNA transcription, a rate-limiting step for ribosome biogenesis, in a dose-dependent manner. Amodiaquine triggers degradation of the catalytic subunit of RNA polymerase I (Pol I), with ensuing RPL5/RPL11-dependent stabilization of p53. Pol I shutdown occurs in the absence of DNA damage and without the subsequent ATM-dependent inhibition of rRNA transcription. RNAseq analysis revealed mechanistic similarities of amodiaquine with BMH-21, the first-in-class Pol I inhibitor, and with chloroquine, the antimalarial analog of amodiaquine, with well-established autophagy-inhibitory activity. Interestingly, autophagy inhibition caused by amodiaquine is not involved in the inhibition of rRNA transcription, suggesting two independent anticancer mechanisms. In vitro, amodiaquine is more efficient than chloroquine in restraining the proliferation of human cell lines derived from colorectal carcinomas, a cancer type with predicted susceptibility to ribosome biogenesis stress. Taken together, our data reveal an unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy.", "doi": "10.1038/s41418-019-0387-5", "pmid": "31285544", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41418-019-0387-5"}, {"db": "pmc", "key": "PMC7205879"}], "notes": [], "created": "2019-11-28T13:50:15.354Z", "modified": "2025-10-17T13:04:28.370Z"}]}