{"entity": "researcher", "timestamp": "2026-08-20T20:54:29.975Z", "family": "Munk", "given": "Sebastian Howen Nesgaard", "initials": "SHN", "orcid": "0000-0002-4601-4833", "affiliations": ["DNA Replication and Cancer Group, Danish Cancer Institute, Copenhagen, Denmark."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c30767aaac5401696179217992498a0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c30767aaac5401696179217992498a0"}}, "publications": [{"entity": "publication", "iuid": "6703dfab66c94278856a80aba8102dc7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7"}}, "title": "NAD+ regulates nucleotide metabolism and genomic DNA replication.", "authors": [{"family": "Munk", "given": "Sebastian Howen Nesgaard", "initials": "SHN", "orcid": "0000-0002-4601-4833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c30767aaac5401696179217992498a0.json"}}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Adelantado Rubio", "given": "Alba", "initials": "A"}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Pappas", "given": "George", "initials": "G"}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Lee", "given": "MyungHee", "initials": "M"}, {"family": "Johnsen", "given": "Lea Gi\u00f8rtz", "initials": "LG", "orcid": "0000-0002-0744-0899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ddbbcb25f0b54c0288252fc69b1d53d9.json"}}, {"family": "Guldberg", "given": "Per", "initials": "P"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "25", "issue": "12", "pages": "1774-1786", "issn-l": "1465-7392"}, "abstract": "The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb's cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb's cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.", "doi": "10.1038/s41556-023-01280-z", "pmid": "37957325", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10709141"}, {"db": "pii", "key": "10.1038/s41556-023-01280-z"}], "notes": [], "created": "2026-08-20T08:55:00.963Z", "modified": "2026-08-20T08:55:01.154Z"}]}