{"entity": "researcher", "timestamp": "2026-08-20T21:36:35.616Z", "family": "Maynard", "given": "Scott", "initials": "S", "orcid": "0000-0001-5625-936X", "affiliations": ["Danish Cancer Society Research Center, Copenhagen, Denmark."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c"}}, "publications": [{"entity": "publication", "iuid": "7d790256dedb49e79dd2a8f355a9f954", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7d790256dedb49e79dd2a8f355a9f954.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7d790256dedb49e79dd2a8f355a9f954"}}, "title": "Lamin A/C impairments cause mitochondrial dysfunction by attenuating PGC1\u03b1 and the NAMPT-NAD+ pathway.", "authors": [{"family": "Maynard", "given": "Scott", "initials": "S", "orcid": "0000-0001-5625-936X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c.json"}}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Galanos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-1403-4685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d1071fd28cb42d6b328182cddfd341f.json"}}, {"family": "Rizza", "given": "Salvatore", "initials": "S"}, {"family": "Yamamoto", "given": "Tatsuro", "initials": "T"}, {"family": "Gram", "given": "Helena Hagner", "initials": "HH"}, {"family": "Munk", "given": "Sebastian H N", "initials": "SHN"}, {"family": "Shoaib", "given": "Muhammad", "initials": "M", "orcid": "0000-0003-1296-5005", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a90b52fbd71d432982b9807804e881f2.json"}}, {"family": "S\u00f8rensen", "given": "Claus Storgaard", "initials": "CS"}, {"family": "Bohr", "given": "Vilhelm A", "initials": "VA", "orcid": "0000-0003-4823-6429", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57e81811b78745cc842862146c6ee7b2.json"}}, {"family": "Lerdrup", "given": "Mads", "initials": "M"}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}], "type": "journal article", "published": "2022-09-23", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "50", "issue": "17", "pages": "9948-9965", "issn-l": "0305-1048"}, "abstract": "Mutations in the lamin A/C gene (LMNA) cause laminopathies such as the premature aging Hutchinson Gilford progeria syndrome (HGPS) and altered lamin A/C levels are found in diverse malignancies. The underlying lamin-associated mechanisms remain poorly understood. Here we report that lamin A/C-null mouse embryo fibroblasts (Lmna-/- MEFs) and human progerin-expressing HGPS fibroblasts both display reduced NAD+ levels, unstable mitochondrial DNA and attenuated bioenergetics. This mitochondrial dysfunction is associated with reduced chromatin recruitment (Lmna-/- MEFs) or low levels (HGPS) of PGC1\u03b1, the key transcription factor for mitochondrial homeostasis. Lmna-/- MEFs showed reduced expression of the NAD+-biosynthesis enzyme NAMPT and attenuated activity of the NAD+-dependent deacetylase SIRT1. We find high PARylation in lamin A/C-aberrant cells, further decreasing the NAD+ pool and consistent with impaired DNA base excision repair in both cell models, a condition that fuels DNA damage-induced PARylation under oxidative stress. Further, ATAC-sequencing revealed a substantially altered chromatin landscape in Lmna-/- MEFs, including aberrantly reduced accessibility at the Nampt gene promoter. Thus, we identified a new role of lamin A/C as a key modulator of mitochondrial function through impairments of PGC1\u03b1 and the NAMPT-NAD+ pathway, with broader implications for the aging process.", "doi": "10.1093/nar/gkac741", "pmid": "36099415", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9508839"}, {"db": "pii", "key": "6696852"}], "notes": [], "created": "2026-08-20T09:49:53.952Z", "modified": "2026-08-20T09:49:54.099Z"}, {"entity": "publication", "iuid": "5ea43ffa349f444181e1acfaacf914ed", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ea43ffa349f444181e1acfaacf914ed.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ea43ffa349f444181e1acfaacf914ed"}}, "title": "The human nucleoporin Tpr protects cells from RNA-mediated replication stress.", "authors": [{"family": "Kosar", "given": "Martin", "initials": "M", "orcid": "0000-0002-9400-2327", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21ca71e4ec374b618abe9722627ecf2d.json"}}, {"family": "Giannattasio", "given": "Michele", "initials": "M", "orcid": "0000-0001-7099-5718", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d1b94f91381249bb83cc9742c7edd4b4.json"}}, {"family": "Piccini", "given": "Daniele", "initials": "D", "orcid": "0000-0001-9200-8496", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/468948352ff146beb99dc430b9f153b6.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Garc\u00eda-Ben\u00edtez", "given": "Francisco", "initials": "F"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Barroso", "given": "Sonia I", "initials": "SI", "orcid": "0000-0002-0062-2016", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/37a0b52bdbe64a1c884d5e02c49927ff.json"}}, {"family": "Gaillard", "given": "H\u00e9l\u00e8ne", "initials": "H", "orcid": "0000-0002-5740-0641", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961deb0e44d5438ca505c21a45526ec6.json"}}, {"family": "Martini", "given": "Emanuele", "initials": "E", "orcid": "0000-0002-3375-7726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04481a4fe5eb4fa28409b51f4333cfae.json"}}, {"family": "Restuccia", "given": "Umberto", "initials": "U"}, {"family": "Ramirez-Otero", "given": "Miguel Angel", "initials": "MA", "orcid": "0000-0001-8428-1150", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/20745976fd6f4c59831c9c78d5069a9b.json"}}, {"family": "Garre", "given": "Massimiliano", "initials": "M"}, {"family": "Verga", "given": "Eleonora", "initials": "E"}, {"family": "And\u00fajar-S\u00e1nchez", "given": "Miguel", "initials": "M", "orcid": "0000-0002-4858-6915", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e4670566116349baaf46842b74fc8c2d.json"}}, {"family": "Maynard", "given": "Scott", "initials": "S", "orcid": "0000-0001-5625-936X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c.json"}}, {"family": "Hodny", "given": "Zdenek", "initials": "Z"}, {"family": "Costanzo", "given": "Vincenzo", "initials": "V"}, {"family": "Kumar", "given": "Amit", "initials": "A", "orcid": "0000-0003-1732-440X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fa80f08c954440a9cadd6dce14a7528.json"}}, {"family": "Bachi", "given": "Angela", "initials": "A", "orcid": "0000-0003-4842-6556", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22f10333c9b3498cb8805d5b9352898f.json"}}, {"family": "Aguilera", "given": "Andr\u00e9s", "initials": "A", "orcid": "0000-0003-4782-1714", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/813e18ed79fb4c53b9a22fb1ac76b3c0.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Foiani", "given": "Marco", "initials": "M", "orcid": "0000-0003-4795-834X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/374821b873e6444c975d79c5a1f309ea.json"}}], "type": "journal article", "published": "2021-06-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "3937", "issn-l": "2041-1723"}, "abstract": "Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress. Tpr deficiency evokes enhanced levels of DNA-RNA hybrids. Additionally, complementary proteomic strategies identify a network of Tpr-interacting proteins mediating RNA processing, such as MATR3 and SUGP2, and functional experiments confirm that their depletion trigger cellular phenotypes shared with Tpr deficiency. Mechanistic studies reveal the interplay of Tpr with GANP, a component of the TREX-2 complex. The Tpr-GANP interaction is supported by their shared protein level alterations in a cohort of ovarian carcinomas. Our results reveal links between nucleoporins, DNA transcription and replication, and the existence of a network physically connecting replication forks with transcription, splicing, and mRNA export machinery.", "doi": "10.1038/s41467-021-24224-3", "pmid": "34168151", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8225803"}, {"db": "pii", "key": "10.1038/s41467-021-24224-3"}], "notes": [], "created": "2026-08-20T08:51:33.116Z", "modified": "2026-08-20T08:51:33.756Z"}]}