Nuclear localization and in situ DNA damage by Mycobacterium tuberculosis nucleoside-diphosphate kinase.

The Journal of Biological Chemistry
Adesh Kumar SainiVibha Tandon

Abstract

Nucleoside-diphosphate kinase of Mycobacterium tuberculosis (mNdK) is a secretory protein, but the rationale behind secreting an enzyme involved in the maintenance of cellular pool of nucleoside triphosphates is not clearly understood. To elucidate the biological significance of mNdK secretion, we expressed mNdK fused to green fluorescent protein in HeLa and COS-1 cells. Interestingly, mNdK was detected in the nuclei of HeLa and COS-1 cells. Incubation of mNdK with nuclei isolated from HeLa and COS-1 cells led to in situ damage of chromosomal DNA. Surface plasmon resonance studies demonstrated that mNdK binds supercoiled plasmid DNA lacking apurinic/apyrimidinic sites with a dissociation constant of 30 +/- 3.2 mum. Plasmid cleavage by mNdK was found to be dependent on the specific divalent metal ion and inhibited by a metal ion chelator. Moreover, the metal ion-dependent DNA cleavage by mNdK was mediated by superoxide radicals as detected by electron paramagnetic resonance. The cleavage reaction was inhibited under nitrogen atmosphere confirming the necessity of molecular oxygen for DNA cleavage. In view of the findings that mNdK is secreted by intracellular mycobacteria and damages the nuclear DNA, it can be postulated that mN...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Jun 19, 1986·Biochimica Et Biophysica Acta·W KorytowskiR C Sealy
Apr 6, 1988·Journal of the National Cancer Institute·P S SteegM E Sobel
Mar 1, 1980·Archives of Biochemistry and Biophysics·E FinkelsteinE J Rauckman
May 25, 1995·Nucleic Acids Research·P J McHugh, J Knowland
Feb 1, 1993·Journal of Bacteriology·J Muñoz-DoradoM Inouye
Jul 1, 1997·Nature Structural Biology·J H CateJ A Doudna
Feb 7, 1998·The Journal of Biological Chemistry·G PanayotouR Savva
Aug 19, 2000·Infection and Immunity·V PunjA M Chakrabarty
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·E H PostelS Kyin
Jan 5, 2002·Journal of Bioenergetics and Biomembranes·J JaninJ Cherfils
Jan 5, 2002·Journal of Bioenergetics and Biomembranes·M L LacombeD O Lambeth
Feb 13, 2003·European Journal of Biochemistry·Puneet ChopraYogendra Singh
Jul 15, 2003·Nature Structural Biology·Tzvi AvivCraig A Smibert
Oct 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Edith H Postel, Bozena M Abramczyk
Nov 18, 2003·Molecular Microbiology·Ramandeep SinghAnil K Tyagi
Apr 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Samuel E BennettDale W Mosbaugh

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Citations

Dec 18, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Gauri MisraRavishankar Ramachandran
Mar 29, 2014·Lung India : Official Organ of Indian Chest Society·Ramanjula C ReddyR Narasimhan
Jan 31, 2014·Surgical Infections·Faten LimaiemSabeh Mzabi
May 28, 2010·QJM : Monthly Journal of the Association of Physicians·M E FalagasP Kopterides
Sep 1, 2006·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Arthur H C de OliveiraRichard J Ward
May 24, 2011·Enzyme Research·Claudio A PereiraMariana R Miranda
Jun 26, 2010·The Biochemical Journal·Haider Hussain Dar, Pradip K Chakraborti
May 3, 2016·International Journal of Molecular Sciences·Hui ZhangAizhen Guo
Oct 28, 2005·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Jun 25, 2015·Microbiology Spectrum·Digby F WarnerValerie Mizrahi

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