Photocrosslinking of G‐Quadruplex‐Forming Sequences found in Human Promoters

Jillian E. Smith-Carpenter, John-Stephen Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

<p> While is it well known that human telomeric DNA sequences can adopt G&hyphen;quadruplex structures, some promoters sequences have also been found to form G&hyphen;quadruplexes, and over 40% of promoters contain putative G&hyphen;quadruplex&hyphen;forming sequences. Because UV light has been shown to crosslink human telomeric G&hyphen;quadruplexes by cyclobutane pyrimidine dimer (CPD) formation between T's on adjacent loops, UV light might also be able to photocrosslink G&hyphen;quadruplexes in promoters. To investigate this possibility, 15 potentially UV&hyphen;crosslinkable G&hyphen;quadruplex&hyphen;forming sequences found in a search of human DNA promoters were UVB irradiated <em> in vitro </em> , and three were confirmed to have formed nonadjacent CPDs by mass spectrometry. In addition to nonadjacent T=T CPDs found in human telomeric DNA, a nonadjacent T=U CPD was discovered that presumably arose from deamination of a nonadjacent T=C CPD. Analysis of the three sequences by circular dichroism, melting temperature analysis and chemical footprinting confirmed the presence of G&hyphen;quadruplexes that could explain the formation of the nonadjacent CPDs. The formation of nonadjacent CPDs from the sequences <em> in vitro </em> suggests that they might be useful probes for the presence of non&hyphen;B DNA structures, such as G&hyphen;quadruplexes, <em> in vivo </em> , and if they were to form <em> in vivo, </em> might also have significant biological consequences.</p>
Original languageAmerican English
JournalPhotochemistry and photobiology
Volume95
DOIs
StatePublished - Jan 1 2019

Disciplines

  • Chemistry
  • Physical Sciences and Mathematics

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