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Article

The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage

1
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
2
Division of Molecular Biology, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2363; https://doi.org/10.3390/ijms21072363
Received: 23 December 2019 / Revised: 20 March 2020 / Accepted: 26 March 2020 / Published: 29 March 2020
Nucleoside diphosphate kinases (NDPK/NME/Nm23) are enzymes composed of subunits NME1/NDPK A and NME2/NDPK B, responsible for the maintenance of the cellular (d)NTP pool and involved in other cellular processes, such as metastasis suppression and DNA damage repair. Although eukaryotic NDPKs are active only as hexamers, it is unclear whether other NME functions require the hexameric form, and how the isoenzyme composition varies in different cellular compartments. To examine the effect of DNA damage on intracellular localization of NME1 and NME2 and the composition of NME oligomers in the nucleus and the cytoplasm, we used live-cell imaging and the FRET/FLIM technique. We showed that exogenous NME1 and NME2 proteins co-localize in the cytoplasm of non-irradiated cells, and move simultaneously to the nucleus after gamma irradiation. The FRET/FLIM experiments imply that, after DNA damage, there is a slight shift in the homomer/heteromer balance between the nucleus and the cytoplasm. Collectively, our results indicate that, after irradiation, NME1 and NME2 engage in mutual functions in the nucleus, possibly performing specific functions in their homomeric states. Finally, we demonstrated that fluorophores fused to the N-termini of NME polypeptides produce the largest FRET effect and thus recommend this orientation for use in similar studies. View Full-Text
Keywords: NME; NDPK; Nm23; nucleoside diphosphate kinase; FRET; FLIM; live-cell imaging NME; NDPK; Nm23; nucleoside diphosphate kinase; FRET; FLIM; live-cell imaging
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MDPI and ACS Style

Radić, M.; Šoštar, M.; Weber, I.; Ćetković, H.; Slade, N.; Herak Bosnar, M. The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage. Int. J. Mol. Sci. 2020, 21, 2363. https://doi.org/10.3390/ijms21072363

AMA Style

Radić M, Šoštar M, Weber I, Ćetković H, Slade N, Herak Bosnar M. The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage. International Journal of Molecular Sciences. 2020; 21(7):2363. https://doi.org/10.3390/ijms21072363

Chicago/Turabian Style

Radić, Martina, Marko Šoštar, Igor Weber, Helena Ćetković, Neda Slade, and Maja Herak Bosnar. 2020. "The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage" International Journal of Molecular Sciences 21, no. 7: 2363. https://doi.org/10.3390/ijms21072363

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