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dc.contributor.authorPuts, Gemma
dc.contributor.authorJarrett, Stuart
dc.contributor.authorLeonard, Mary
dc.contributor.authorMatsangos, Nicolette
dc.contributor.authorSnyder, Devin
dc.contributor.authorWang, Ying
dc.contributor.authorVincent, Richard
dc.contributor.authorPortney, Benjamin
dc.contributor.authorAbbotts, Rachel
dc.contributor.authorMcLaughlin, Lena
dc.contributor.authorZalzman, Michal
dc.contributor.authorRassool, Feyruz
dc.contributor.authorKaetzel, David
dc.date.accessioned2020-09-01T17:13:39Z
dc.date.available2020-09-01T17:13:39Z
dc.date.issued2020-08-02
dc.identifier.urihttp://hdl.handle.net/10713/13614
dc.description.abstractReduced 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.en_US
dc.description.urihttps://doi.org/10.3390/ijms21165896en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.subjectCanceren_US
dc.subjectDNA double strand break repairen_US
dc.subjectDNA repairen_US
dc.subjectHoming endonucleaseen_US
dc.subjectHomologous recombinationen_US
dc.subjectMelanomaen_US
dc.subjectMetastasisen_US
dc.subjectNon-homologous end-joiningen_US
dc.titleMetastasis suppressor nme1 modulates choice of double-strand break repair pathways in melanoma cells by enhancing alternative nhej while inhibiting nhej and hren_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms21165896
dc.identifier.scopusidSCOPUS_ID:85089671168
dc.source.volume21
dc.source.issue16
dc.source.beginpage1
dc.source.endpage15


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