Title

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

Document Type

Article

Publication Date

2019

Abstract

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, 15 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 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‐quadruplexes that could explain the formation of the nonadjacent CPDs. The formation of nonadjacent 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.

Comments

Copyright 2019 The American Society of Photobiology

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Publication Title

Photochemistry and photobiology

Published Citation

Smith‐Carpenter, J. E., & Taylor, J. S. (2019). Photocrosslinking of G‐Quadruplex‐Forming Sequences found in Human Promoters. Photochemistry and photobiology, 95(1), 252-266. https://doi.org/10.1111/php.12991

DOI

10.1111/php.12991

Peer Reviewed

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