6ZX6

Antiparallel basket-type G-quadruplex DNA structure formed in human Bcl-2 promoter containing 8-oxoG

Summary for 6ZX6

• Entry DOI: 10.2210/pdb6zx6/pdb
• NMR Information: BMRB: 34542
• Descriptor: bcl2ex-oxoG19 (1 entity in total)
• Functional Keywords: bcl2, g-quadruplex, oxidative stress, 8-oxo-guanine, promoter, dna
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 7977.10

Authors

Bielskute, S.,Plavec, J.,Podbevsek, P. (deposition date: 2020-07-29, release date: 2021-03-10, Last modification date: 2024-06-19)

Primary citation

Bielskute, S.,Plavec, J.,Podbevsek, P.
Oxidative lesions modulate G-quadruplex stability and structure in the human BCL2 promoter.
Nucleic Acids Res., 49:2346-2356, 2021

PubMed Abstract: 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.

PubMed: 33638996
DOI: 10.1093/nar/gkab057

Experimental method

SOLUTION NMR