Jettison-MS of nucleic acid species Journal Article


Authors: Wang, P.; Shah, G. L.; Landau, H.; Coulter, M. E.; Walsh, C. A.; Roider, E.; Kramer, C. S.; Beuning, P. J.; Giese, R. W.
Article Title: Jettison-MS of nucleic acid species
Abstract: While MALDI-MS of intact genomic DNA is unheard of, actually many DNA adducts can be detected in this way under certain MALDI conditions: relatively high molar ratio of DNA nucleobases to matrix (0.01 to 0.3), hot matrix (CCA), and high laser fluence. This is because many DNA adducts create "bubbles" on dsDNA (disruption of base pairing), making it easier for these adducts as modified nucleobases to be jettisoned by the laser-derived energy of MALDI (jettison mass spectrometry or JeMS). The method also works for other nucleic acid species, namely nucleobases, nucleosides, nucleotides, and RNA. Examples of what we have detected in this way are as follows: methyladenine in E. coli DNA, 5-hydroxymethylcytosine in human brain DNA, melphalan-adenine in leukocyte DNA from patients on corresponding chemotherapy, wybutosine in tRNA, benzyl DNA adducts in E. coli cell culture treated with benzyl bromide, and various DNA adducts formed in test tube exposure experiments with calf thymus DNA. Noteworthy, in the chemotherapy study, principle component analysis of the data encourages the hypothesis that patient DNA undergoes much more damage than just melphalan adducts. Overall, our work leads to the preliminary generalization that about 5 fmol of a nucleobase deficient in base pairing, and present in a MALDI spot, will be detected by JeMS (on the equipment that we used), irrespective of the type of nucleic acid species which houses it, as long as the nucleobase is relatively basic such as A, C, or G.
Keywords: dna; modified oligonucleotides; epoxide
Journal Title: Journal of the American Society for Mass Spectrometry
Volume: 31
Issue: 8
ISSN: 1044-0305
Publisher: Springer  
Date Published: 2020-08-05
Start Page: 1641
End Page: 1646
Language: English
ACCESSION: WOS:000558798200004
DOI: 10.1021/jasms.0c00084
PROVIDER: wos
PUBMED: 32551641
Notes: Article -- Source: Wos
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  1. Heather Jolie Landau
    419 Landau
  2. Gunjan Lalitchandra Shah
    418 Shah