{"entity": "researcher", "timestamp": "2026-08-23T22:15:13.056Z", "family": "Houseley", "given": "Jonathan", "initials": "J", "orcid": "0000-0001-8509-1500", "affiliations": ["Epigenetics Programme, The Babraham Institute, Cambridge, UK. Jon.houseley@babraham.ac.uk."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8769a63503044b4ad8edc854a1ea989.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8769a63503044b4ad8edc854a1ea989"}}, "publications": [{"entity": "publication", "iuid": "dcf3e5887c984ccdafed6ce567de0353", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/dcf3e5887c984ccdafed6ce567de0353.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/dcf3e5887c984ccdafed6ce567de0353"}}, "title": "The adaptive potential of circular DNA accumulation in ageing cells.", "authors": [{"family": "Hull", "given": "Ryan M", "initials": "RM", "orcid": "0000-0001-7153-4198", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4adfcc02af0b422aa81206bf3c56471d.json"}}, {"family": "Houseley", "given": "Jonathan", "initials": "J", "orcid": "0000-0001-8509-1500", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8769a63503044b4ad8edc854a1ea989.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Curr. Genet.", "issn": "1432-0983", "volume": "66", "issue": "5", "pages": "889-894", "issn-l": "0172-8083"}, "abstract": "Carefully maintained and precisely inherited chromosomal DNA provides long-term genetic stability, but eukaryotic cells facing environmental challenges can benefit from the accumulation of less stable DNA species. Circular DNA molecules lacking centromeres segregate randomly or asymmetrically during cell division, following non-Mendelian inheritance patterns that result in high copy number instability and massive heterogeneity across populations. Such circular DNA species, variously known as extrachromosomal circular DNA (eccDNA), microDNA, double minutes or extrachromosomal DNA (ecDNA), are becoming recognised as a major source of the genetic variation exploited by cancer cells and pathogenic eukaryotes to acquire drug resistance. In budding yeast, circular DNA molecules derived from the ribosomal DNA (ERCs) have been long known to accumulate with age, but it is now clear that aged yeast also accumulate other high-copy protein-coding circular DNAs acquired through both random and environmentally-stimulated recombination processes. Here, we argue that accumulation of circular DNA provides a reservoir of heterogeneous genetic material that can allow rapid adaptation of aged cells to environmental insults, but avoids the negative fitness impacts on normal growth of unsolicited gene amplification in the young population.", "doi": "10.1007/s00294-020-01069-9", "pmid": "32296868", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7497353"}, {"db": "pii", "key": "10.1007/s00294-020-01069-9"}], "notes": [], "created": "2026-08-21T11:06:29.239Z", "modified": "2026-08-21T11:06:29.326Z"}, {"entity": "publication", "iuid": "68a4ec661d494db1be3dae01e12f22d6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/68a4ec661d494db1be3dae01e12f22d6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/68a4ec661d494db1be3dae01e12f22d6"}}, "title": "Transcription-induced formation of extrachromosomal DNA during yeast ageing.", "authors": [{"family": "Hull", "given": "Ryan M", "initials": "RM", "orcid": "0000-0001-7153-4198", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4adfcc02af0b422aa81206bf3c56471d.json"}}, {"family": "King", "given": "Michelle", "initials": "M"}, {"family": "Pizza", "given": "Grazia", "initials": "G"}, {"family": "Krueger", "given": "Felix", "initials": "F", "orcid": "0000-0002-5513-3324", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd6dfb32175e48b9870fa0d4cf112bed.json"}}, {"family": "Vergara", "given": "Xabier", "initials": "X", "orcid": "0000-0002-9521-0881", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ca1fb48dc9848b9928dc4c7a45e0016.json"}}, {"family": "Houseley", "given": "Jonathan", "initials": "J", "orcid": "0000-0001-8509-1500", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8769a63503044b4ad8edc854a1ea989.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "17", "issue": "12", "pages": "e3000471", "issn-l": "1544-9173"}, "abstract": "Extrachromosomal circular DNA (eccDNA) facilitates adaptive evolution by allowing rapid and extensive gene copy number variation and is implicated in the pathology of cancer and ageing. Here, we demonstrate that yeast aged under environmental copper accumulate high levels of eccDNA containing the copper-resistance gene CUP1. Transcription of the tandemly repeated CUP1 gene causes CUP1 eccDNA accumulation, which occurs in the absence of phenotypic selection. We have developed a sensitive and quantitative eccDNA sequencing pipeline that reveals CUP1 eccDNA accumulation on copper exposure to be exquisitely site specific, with no other detectable changes across the eccDNA complement. eccDNA forms de novo from the CUP1 locus through processing of DNA double-strand breaks (DSBs) by Sae2, Mre11 and Mus81, and genome-wide analyses show that other protein coding eccDNA species in aged yeast share a similar biogenesis pathway. Although abundant, we find that CUP1 eccDNA does not replicate efficiently, and high-copy numbers in aged cells arise through frequent formation events combined with asymmetric DNA segregation. The transcriptional stimulation of CUP1 eccDNA formation shows that age-linked genetic change varies with transcription pattern, resulting in gene copy number profiles tailored by environment.", "doi": "10.1371/journal.pbio.3000471", "pmid": "31794573", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6890164"}, {"db": "pii", "key": "PBIOLOGY-D-19-02355"}], "notes": [], "created": "2026-08-21T12:43:31.347Z", "modified": "2026-08-21T12:43:31.477Z"}]}