{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:31:50Z","timestamp":1772209910697,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The cell cycle and the transcriptome dynamics of yeast exposed to extracellular self-DNA during an aerobic batch culture on glucose have been investigated using cytofluorimetric and RNA-seq analyses. In parallel, the same study was conducted on yeast cells growing in the presence of (heterologous) nonself-DNA. The self-DNA treatment determined a reduction in the growth rate and a major elongation of the diauxic lag phase, as well as a significant delay in the achievement of the stationary phase. This was associated with significant changes in the cell cycle dynamics, with slower exit from the G0 phase, followed by an increased level of cell percentage in the S phase, during the cultivation. Comparatively, the exposure to heterologous DNA did not affect the growth curve and the cell cycle dynamics. The transcriptomic analysis showed that self-DNA exposure produced a generalized downregulation of transmembrane transport and an upregulation of genes associated with sulfur compounds and the pentose phosphate pathway. Instead, in the case of the nonself treatment, a clear response to nutrient deprivation was detected. Overall, the presented findings represent further insights into the complex functional mechanisms of self-DNA inhibition.<\/jats:p>","DOI":"10.3390\/biom14060663","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T06:40:26Z","timestamp":1717656026000},"page":"663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extracellular Self-DNA Effects on Yeast Cell Cycle and Transcriptome during Batch Growth"],"prefix":"10.3390","volume":"14","author":[{"given":"Emanuela","family":"Palomba","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Bioresources CNR, Via Universit\u00e0 133, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-7132","authenticated-orcid":false,"given":"Maria Luisa","family":"Chiusano","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Monticolo","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"},{"name":"Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Langella","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0 (ISS) Core Facilities, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Tirelli","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0 (ISS) Core Facilities, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-3961","authenticated-orcid":false,"given":"Elisabetta","family":"de Alteriis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u201cFederico II\u201d, Via Cinthia 26, 80126 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Iannaccone","sequence":"additional","affiliation":[{"name":"Laboratory of Bioproducts and Bioprocesses ENEA, Piazzale Enrico Fermi 1, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-0901","authenticated-orcid":false,"given":"Pasquale","family":"Termolino","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Bioresources CNR, Via Universit\u00e0 133, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Capparelli","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-1132","authenticated-orcid":false,"given":"Fabrizio","family":"Carteni","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-8708","authenticated-orcid":false,"given":"Guido","family":"Incerti","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, Via delle Scienze 206, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-2625","authenticated-orcid":false,"given":"Stefano","family":"Mazzoleni","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples \u201cFederico II\u201d, Via Universit\u00e0 100, 80055 Portici, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Mechanisms and Regulation of Extracellular DNA Release and Its Biological Roles in Microbial Communities","volume":"8","author":"Zafra","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1007\/s00253-018-8786-y","article-title":"The use of extracellular DNA as a proxy for specific microbial activity","volume":"102","author":"Nagler","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"589837","DOI":"10.3389\/fpls.2020.589837","article-title":"The Role of DNA in the Extracellular Environment: A Focus on NETs, RETs and Biofilms","volume":"11","author":"Monticolo","year":"2020","journal-title":"Front. Plant Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/bit.27760","article-title":"V The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms","volume":"118","author":"Panlilio","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zafra, O., Lamprecht-Grand\u00edo, M., de Figueras, C.G., and Gonz\u00e1lez-Pastor, J.E. (2012). Extracellular DNA release by undomesticated Bacillus subtilis is regulated by early competence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048716"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1111\/j.1365-2958.2005.05008.x","article-title":"A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms","volume":"59","author":"Barken","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1111\/j.1365-2958.2005.04521.x","article-title":"Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system","volume":"55","author":"Hamilton","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/1574-6941.12168","article-title":"Extracellular DNA in adhesion and biofilm formation of four environmental isolates: A quantitative study","volume":"86","author":"Tang","year":"2013","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/1040841X.2013.841639","article-title":"The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms","volume":"41","author":"Okshevsky","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e01333-14","DOI":"10.1128\/mBio.01333-14","article-title":"Novel entries in a fungal biofilm matrix encyclopedia","volume":"5","author":"Zarnowski","year":"2014","journal-title":"mBio"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1128\/EC.00287-12","article-title":"Extracellular DNA release acts as an antifungal resistance mechanism in mature Aspergillus fumigatus biofilms","volume":"12","author":"Rajendran","year":"2013","journal-title":"Eukaryot. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12934-015-0295-4","article-title":"A novel process-based model of microbialgrowth: Self-inhibition in Saccharomyces cerevisiae aerobic fed-batch cultures","volume":"14","author":"Mazzoleni","year":"2015","journal-title":"Microb. Cell Fact."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/nph.13306","article-title":"Inhibitory effects of extracellular self-DNA: A general biological process?","volume":"206","author":"Mazzoleni","year":"2015","journal-title":"New Phytol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Palomba, E., Chiaiese, P., Termolino, P., Paparo, R., Filippone, E., Mazzoleni, S., and Chiusano, M.L. (2022). Effects of Extracellular Self- and Nonself-DNA on the Freshwater Microalga Chlamydomonas reinhardtii and on the Marine Microalga Nannochloropsis gaditana. Plants, 11.","DOI":"10.3390\/plants11111436"},{"key":"ref_15","first-page":"292","article-title":"Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation","volume":"10","author":"Incerti","year":"2023","journal-title":"Microb. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0005-2787(69)90273-1","article-title":"Chromatography of nucleic acids on hydroxyapatite. I. Chromatography of native DNA","volume":"174","author":"Bernardi","year":"1969","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0021-9673(00)87048-X","article-title":"Rapid isolation of carcinogen-bound DNA and RNA by hydroxyapatite chromatography","volume":"174","author":"Beland","year":"1979","journal-title":"J. Chromatogr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5039","DOI":"10.1128\/AEM.00204-10","article-title":"Hydroxyapatite-mediated separation of double-stranded DNA, single-stranded DNA, and RNA genomes from natural viral assemblages","volume":"76","author":"Fadrosh","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00414585","article-title":"Energetics of the budding cycle of Saccharomyces cerevisiae during glucose limited aerobic growth","volume":"66","year":"1969","journal-title":"Arch. Mikrobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1089\/omi.2010.0069","article-title":"Transcriptional regulation in yeast during diauxic shift and stationary phase","volume":"14","author":"Galdieri","year":"2010","journal-title":"OMICS"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev.mi.03.100149.002103","article-title":"THE GROWTH OF BACTERIAL CULTURES","volume":"3","author":"Monod","year":"1949","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/yea.320080703","article-title":"Effect of benzoic acid on metabolic fluxes in yeasts: A continuous-culture study on the regulation of respiration and alcoholic fermentation","volume":"8","author":"Verduyn","year":"1992","journal-title":"Yeast"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1128\/AEM.68.5.2095-2100.2002","article-title":"Auxotrophic yeast strains in fundamental and applied research","volume":"68","author":"Pronk","year":"2002","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Palomba, E., Tirelli, V., de Alteriis, E., Parascandola, P., Landi, C., Mazzoleni, S., and Sanchez, M. (2021). A cytofluorimetric analysis of a Saccharomyces cerevisiae population cultured in a fed-batch bioreactor. PLoS ONE, 16.","DOI":"10.1101\/2021.02.26.433019"},{"key":"ref_25","unstructured":"Andrews, S. (2024, January 15). FastQC: A Quality Control Tool for High Throughput Sequence Data 2010. Available online: https:\/\/www.bibsonomy.org\/bibtex\/f230a919c34360709aa298734d63dca3."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkt214","article-title":"The Subread aligner: Fast, accurate and scalable read mapping by seed-and-vote","volume":"41","author":"Liao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W193","DOI":"10.1093\/nar\/gkm226","article-title":"g:Profiler--a web-based toolset for functional profiling of gene lists from large-scale experiments","volume":"35","author":"Reimand","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.molcel.2019.06.039","article-title":"One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages","volume":"75","author":"Yu","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.molcel.2017.02.026","article-title":"A Metabolic Function for Phospholipid and Histone Methylation","volume":"66","author":"Ye","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.1128\/JB.181.24.7405-7408.1999","article-title":"Bacterial growth: Constant obsession with dN\/dt","volume":"181","author":"Neidhardt","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0968-0004(81)90073-6","article-title":"Is Saccharomyces cerevisiae a typical facultative anaerobe?","volume":"6","author":"Lagunas","year":"1981","journal-title":"Trends Biochem. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e01331-18","DOI":"10.1128\/mBio.01331-18","article-title":"The Crabtree Effect Shapes the Saccharomyces cerevisiae Lag Phase during the Switch between Different Carbon Sources","volume":"9","author":"Cerulus","year":"2018","journal-title":"mBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00294-019-00938-2","article-title":"On the duration of the microbial lag phase","volume":"65","author":"Vermeersch","year":"2019","journal-title":"Curr. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0092-8674(95)90481-6","article-title":"A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage","volume":"82","author":"Paulovich","year":"1995","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1042\/BC20090053","article-title":"The S-phase checkpoint: Targeting the replication fork","volume":"101","author":"Segurado","year":"2009","journal-title":"Biol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ciardo, D., Goldar, A., and Marheineke, K. (2019). On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway. Genes, 10.","DOI":"10.3390\/genes10020094"},{"key":"ref_40","first-page":"fow101","article-title":"Signaling pathways of replication stress in yeast","volume":"17","author":"Pardo","year":"2017","journal-title":"FEMS Yeast Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.3390\/biom5032123","article-title":"Managing Single-Stranded DNA during Replication Stress in Fission Yeast","volume":"5","author":"Sabatinos","year":"2015","journal-title":"Biomolecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1747-1028-1-16","article-title":"The yeast ubiquitin ligase SCFMet30: Connecting environmental and intracellular conditions to cell division","volume":"1","author":"Kaiser","year":"2006","journal-title":"Cell Div."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrc3557","article-title":"Serine, glycine and one-carbon units: Cancer metabolism in full circle","volume":"13","author":"Locasale","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2015.08.002","article-title":"Amino acid management in cancer","volume":"43","author":"Tsun","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chiusano, M.L., Incerti, G., Colantuono, C., Termolino, P., Palomba, E., Monticolo, F., Benvenuto, G., Foscari, A., Esposito, A., and Marti, L. (2021). Arabidopsis thaliana Response to Extracellular DNA: Self Versus Nonself Exposure. Plants, 10.","DOI":"10.3390\/plants10081744"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Barbero, F., Guglielmotto, M., Capuzzo, A., and Maffei, M.E. (2016). Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays). Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101659"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3389\/fpls.2021.686121","article-title":"Extracellular Fragmented Self-DNA Is Involved in Plant Responses to Biotic Stress","volume":"12","author":"Barbero","year":"2021","journal-title":"Front. Plant Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113453","DOI":"10.1016\/j.phytochem.2022.113453","article-title":"Metabolomics and molecular networking analyses in Arabidopsis thaliana show that extracellular self-DNA affects nucleoside\/nucleotide cycles with accumulation of cAMP, cGMP and N6-methyl-AMP","volume":"204","author":"Lanzotti","year":"2022","journal-title":"Phytochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Colombo, M., Grauso, L., Lanzotti, V., Incerti, G., Adamo, A., Storlazzi, A., Gigliotti, S., and Mazzoleni, S. (2023). Self-DNA Inhibition in Drosophila melanogaster Development: Metabolomic Evidence of the Molecular Determinants. Biology, 12.","DOI":"10.3390\/biology12111378"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Germoglio, M., Adamo, A., Incerti, G., Carten\u00ec, F., Gigliotti, S., Storlazzi, A., and Mazzoleni, S. (2022). Self-DNA Exposure Induces Developmental Defects and Germline DNA Damage Response in Caenorhabditis elegans. Biology, 11.","DOI":"10.3390\/biology11020262"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/663\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:37Z","timestamp":1760108077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,6]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["biom14060663"],"URL":"https:\/\/doi.org\/10.3390\/biom14060663","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,6]]}}}