Photocrosslinking of G-Quadruplex Forming Sequences found in Human Promoters
| Autor: | John-Stephen Taylor, Jillian E. Smith-Carpenter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Circular dichroism
Stereochemistry Ultraviolet Rays education Deamination Pyrimidine dimer 010402 general chemistry G-quadruplex 01 natural sciences Biochemistry Article Mass Spectrometry 03 medical and health sciences In vivo Humans heterocyclic compounds Physical and Theoretical Chemistry Promoter Regions Genetic 030304 developmental biology 0303 health sciences Chemistry Promoter General Medicine Photochemical Processes Footprinting In vitro 0104 chemical sciences G-Quadruplexes Pyrimidine Dimers |
| Popis: | While is it well known that human telomeric DNA sequences can adopt G-quadruplex structures, some promoters sequences have also been found to form G-quadruplexes, and over 40% of promoters contain putative G-quadruplex forming sequences. Because UV light has been shown to crosslink human telomeric G-quadruplexes by cyclobutane pyrimidine dimer (CPD) formation between T’s on adjacent loops, UV light might also be able to photocrosslink G-quadruplexes in promoters. To investigate this possibility, fifteen potentially UV-crosslinkable G-quadruplex forming sequences found in a search of human DNA promoters, were UVB irradiated in vitro, and three were confirmed to have formed non-adjacent CPDs by mass spectrometry. In addition to non-adjacent T=T CPDs found in human telomeric DNA, a non-adjacent T=U CPD was discovered that presumably arose from deamination of a non-adjacent T=C CPD. Analysis of the three sequences by circular dichroism, melting temperature analysis, and chemical footprinting confirmed the presence of G-quadruplexes that could explain the formation of the non-adjacent CPDs. The formation of non-adjacent CPDs from the sequences in vitro, suggests that they might be useful probes for the presence of non-B DNA structures, such as G-quadruplexes, in vivo, and if they were to form in vivo, might also have significant biological consequences. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|