2022
DOI: 10.1021/acsphyschemau.1c00050
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1H NMR Chemical Exchange Techniques Reveal Local and Global Effects of Oxidized Cytosine Derivatives

Abstract: 5-Carboxycytosine (5caC) is a rare epigenetic modification found in nucleic acids of all domains of life. Despite its sparse genomic abundance, 5caC is presumed to play essential regulatory roles in transcription, maintenance and base-excision processes in DNA. In this work, we utilize nuclear magnetic resonance (NMR) spectroscopy to address the effects of 5caC incorporation into canonical DNA strands at multiple pH and temperature conditions. Our results demonstrate that 5caC has a pH-dependent global destabi… Show more

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Cited by 7 publications
(7 citation statements)
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“…Also the destabilizing effect of the modified nucleobases 5hmC and 5fC are consistent with the literature ,,, and are said to have their origin in increased base pair fluctuations. Effects of 5caC, on the other hand, have been found contradictory in previous publications. ,, Two groups reported no detectable effects of 5caC on the hybrid stability under low monovalent ion concentrations (∼50 mM NaCl). , Similar to our results, a significant stabilizing effect at comparable higher monovalent ion concentrations (∼150 mM NaCl) has been reported . The increased stability of the latter one can be assigned to additional electronic dipole–dipole interactions, as the stacking geometry of the bases seems to remain unchanged in the presence of the carboxyl group.…”
Section: Resultssupporting
confidence: 68%
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“…Also the destabilizing effect of the modified nucleobases 5hmC and 5fC are consistent with the literature ,,, and are said to have their origin in increased base pair fluctuations. Effects of 5caC, on the other hand, have been found contradictory in previous publications. ,, Two groups reported no detectable effects of 5caC on the hybrid stability under low monovalent ion concentrations (∼50 mM NaCl). , Similar to our results, a significant stabilizing effect at comparable higher monovalent ion concentrations (∼150 mM NaCl) has been reported . The increased stability of the latter one can be assigned to additional electronic dipole–dipole interactions, as the stacking geometry of the bases seems to remain unchanged in the presence of the carboxyl group.…”
Section: Resultssupporting
confidence: 68%
“…Effects of 5caC, on the other hand, have been found contradictory in previous publications. 25,43,44 Two groups reported no detectable effects of 5caC on the hybrid stability under low monovalent ion concentrations (∼50 mM NaCl). 25,43 Similar to our results, a significant stabilizing effect at comparable higher monovalent ion concentrations (∼150 mM NaCl) has been reported.…”
Section: Resultsmentioning
confidence: 99%
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“…81 Prior studies have pointed out that CHO ( 5f C) and COOH ( 5ca C) modifications in cytosine change the pK a of the H-bond accepting N3 nitrogen atom that was predicted to cause a weakening of the H-bond for DNA duplexes. 42,43,82 Computational studies performed on such modified cytosine duplex systems report that the calculated isotropic chemical shift of both the imino proton ( 1 H) and nitrogen ( 15 N) shows a correlated change with the increasing or decreasing H-bond distance in the C-G base pair. 48 Geometry optimized and energy minimized structures of C-G pairs predict an increase in the G:N1-H1Á Á ÁN3:C distance upon varying C from 5m C to 5hm C, 5f C, and 5ca C, the longest being for the 5f C-G base pair.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, the weakening of the 5f C-G base-pair propagates beyond the modification site, as reported for DNA F3 , substantiating the previous findings that 5f C destabilizes the whole DNA duplex. 44,82 Thus, measurement of 15 N chemical shifts could proxy as an indicator of strengthening/ weakening akin to the chemical exchange saturation transfer type experiments. This also explains that 5f C containing DNA templates display reduced substrate specificity of dGTP incorporation as observed experimentally.…”
Section: Discussionmentioning
confidence: 99%