Oxidative lesions modulate G-quadruplex stability and structure in the human BCL2 promoter.

Stasė Bielskutė, Janez Plavec, Peter Podbevšek

Nucleic acids research 2021 Feb 26

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Misregulation of BCL2 expression has been observed with many diseases and is associated with cellular exposure to reactive oxygen species. A region upstream of the P1 promoter in the human BCL2 gene plays a major role in regulating transcription. This G/C-rich region is highly polymorphic and capable of forming G-quadruplex structures. Herein we report that an oxidative event simulated with an 8-oxo-7,8-dihydroguanine (oxoG) substitution within a long G-tract results in a reduction of structural polymorphism. Surprisingly, oxoG within a 25-nt construct boosts thermal stability of the resulting G-quadruplex. This is achieved by distinct hydrogen bonding properties of oxoG, which facilitate formation of an antiparallel basket-type G-quadruplex with a three G-quartet core and a G·oxoG·C base triad. While oxoG has previously been considered detrimental for G-quadruplex formation, its stabilizing effect within a promoter described in this study suggests a potential novel regulatory role of oxidative stress in general and specifically in BCL2 gene transcription. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Stasė Bielskutė, Janez Plavec, Peter Podbevšek. Oxidative lesions modulate G-quadruplex stability and structure in the human BCL2 promoter. Nucleic acids research. 2021 Feb 26;49(4):2346-2356