{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:49:07Z","timestamp":1788997747079,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA83237"],"award-info":[{"award-number":["R01 CA83237"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA159871"],"award-info":[{"award-number":["R01 CA159871"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA159871-S1"],"award-info":[{"award-number":["R01 CA159871-S1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32 CA154274"],"award-info":[{"award-number":["T32 CA154274"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R25 GM055036"],"award-info":[{"award-number":["R25 GM055036"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reduced NME1 expression in melanoma cell lines, mouse models of melanoma, and melanoma specimens in human patients is associated with increased metastatic activity. Herein, we investigate the role of NME1 in repair of double-stranded breaks (DSBs) and choice of double-strand break repair (DSBR) pathways in melanoma cells. Using chromatin immunoprecipitation, NME1 was shown to be recruited rapidly and directly to DSBs generated by the homing endonuclease I-PpoI. NME1 was recruited to DSBs within 30 min, in concert with recruitment of ataxia-telangiectasia mutated (ATM) protein, an early step in DSBR complex formation, as well as loss of histone 2B. NME1 was detected up to 5 kb from the break site after DSB induction, suggesting a role in extending chromatin reorganization away from the repair site. shRNA-mediated silencing of NME1 expression led to increases in the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways of double-strand break repair (DSBR), and reduction in the low fidelity, alternative-NHEJ (A-NHEJ) pathway. These findings suggest low expression of NME1 drives DSBR towards higher fidelity pathways, conferring enhanced genomic stability necessary for rapid and error-free proliferation in invasive and metastatic cells. The novel mechanism highlighted in the current study appears likely to impact metastatic potential and therapy-resistance in advanced melanoma and other cancers.<\/jats:p>","DOI":"10.3390\/ijms21165896","type":"journal-article","created":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T06:33:20Z","timestamp":1597646000000},"page":"5896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metastasis Suppressor NME1 Modulates Choice of Double-Strand Break Repair Pathways in Melanoma Cells by Enhancing Alternative NHEJ while Inhibiting NHEJ and HR"],"prefix":"10.3390","volume":"21","author":[{"given":"Gemma","family":"Puts","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Portney","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Abbotts","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-0381","authenticated-orcid":false,"given":"Lena","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-2951","authenticated-orcid":false,"given":"Michal","family":"Zalzman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"},{"name":"Department of Otorhinolaryngology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feyruz","family":"Rassool","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2761-8970","authenticated-orcid":false,"given":"David","family":"Kaetzel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc2594","article-title":"Learning therapeutic lessons from metastasis suppressor proteins","volume":"9","author":"Smith","year":"2009","journal-title":"Nat. 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