• Medientyp: E-Artikel
  • Titel: Photocrosslinking of G‐Quadruplex‐Forming Sequences found in Human Promoters
  • Beteiligte: Smith‐Carpenter, Jillian E.; Taylor, John‐Stephen
  • Erschienen: Wiley, 2019
  • Erschienen in: Photochemistry and Photobiology
  • Sprache: Englisch
  • DOI: 10.1111/php.12991
  • ISSN: 0031-8655; 1751-1097
  • Schlagwörter: Physical and Theoretical Chemistry ; General Medicine ; Biochemistry
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>While is it well known that human telomeric <jats:styled-content style="fixed-case">DNA</jats:styled-content> 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 <jats:styled-content style="fixed-case">UV</jats:styled-content> light has been shown to crosslink human telomeric G‐quadruplexes by cyclobutane pyrimidine dimer (<jats:styled-content style="fixed-case">CPD</jats:styled-content>) formation between T's on adjacent loops, <jats:styled-content style="fixed-case">UV</jats:styled-content> light might also be able to photocrosslink G‐quadruplexes in promoters. To investigate this possibility, 15 potentially <jats:styled-content style="fixed-case">UV</jats:styled-content>‐crosslinkable G‐quadruplex‐forming sequences found in a search of human <jats:styled-content style="fixed-case">DNA</jats:styled-content> promoters were <jats:styled-content style="fixed-case">UVB</jats:styled-content> irradiated <jats:italic>in vitro</jats:italic>, and three were confirmed to have formed nonadjacent <jats:styled-content style="fixed-case">CPD</jats:styled-content>s by mass spectrometry. In addition to nonadjacent T=T <jats:styled-content style="fixed-case">CPD</jats:styled-content>s found in human telomeric <jats:styled-content style="fixed-case">DNA</jats:styled-content>, a nonadjacent T=U <jats:styled-content style="fixed-case">CPD</jats:styled-content> was discovered that presumably arose from deamination of a nonadjacent T=C <jats:styled-content style="fixed-case">CPD</jats:styled-content>. 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 nonadjacent <jats:styled-content style="fixed-case">CPD</jats:styled-content>s. The formation of nonadjacent <jats:styled-content style="fixed-case">CPD</jats:styled-content>s from the sequences <jats:italic>in vitro</jats:italic> suggests that they might be useful probes for the presence of non‐B <jats:styled-content style="fixed-case">DNA</jats:styled-content> structures, such as G‐quadruplexes, <jats:italic>in vivo</jats:italic>, and if they were to form <jats:italic>in vivo,</jats:italic> might also have significant biological consequences.</jats:p>