English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Mutations of the KRAS proto-oncogene are associated with several tumor types, which is why it is being considered as a target for anti-cancer drug development. The human KRAS promoter contains a nuclease hypersensitive element (NHE), which can bind to nuclear proteins and is believed to form G-quadruplex structures. Previous studies showed that a 32-nt oligonucleotide (32R-3n) mimicking the KRAS NHE can reduce gene transcription by sequestering MAZ, a crucial transcription factor. Here we show that 32R-3n has to dimerize in order to fold into a G-quadruplex structure. Individual 5'- and 3'-end G-quadruplex units are formed and both feature a symmetric head-to-head topology with edge-type loops. The MAZ binding sequence is located within the 3'-end unit. Nuclear magnetic resonance data complemented by CD and UV spectra show that nucleotides of the MAZ binding G-rich motif are dynamic and could be available for sequence or structure based recognition. Both stable G-quadruplex structures could protect 5'- and 3'-ends of 32R-3n and enhance its anti-cancer activity. Single stranded genomic KRAS NHE including nucleotides flanking the 32R-3n sequence could favor a different monomeric fold, which remains unknown.

KRASpromoter oligonucleotide with decoy activity dimerizes into a unique topology consisting of two G-quadruplex units