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Biomedicines, volume 10, issue 8, pages 1871

G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions

Publication typeJournal Article
Publication date2022-08-03
Journal: Biomedicines
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor4.7
ISSN22279059
General Biochemistry, Genetics and Molecular Biology
Medicine (miscellaneous)
Abstract

G-quadruplexes (G4s) are a unique class of noncanonical DNAs that play a key role in cellular processes and neoplastic transformation. Herein, we focused on the promoter region of human TERT oncogene, whose product is responsible for the immortality of cancer cells. It has been shown by chemical probing and spectroscopic methods that synthetic 96-nt DNAs modeling the wild-type G-rich strand of the hTERT promoter and its variants with G>A point substitutions corresponding to somatic driver mutations fold into three stacked parallel G4s with sites of local G4 destabilization caused by G>A substitutions in the G4 motif. These models were used to elucidate how the hTERT multiG4 affects the binding affinity and functional responses of two key proteins, MutS and MutL, involved in the initial stage of DNA mismatch repair (MMR) in Escherichiacoli and Neisseriagonorrhoeae with different MMR mechanisms. We have shown for the first time that (i) point substitutions do not affect the effective binding of these proteins to the hTERT G4 structure, and (ii) the endonuclease activity of MutL from N. gonorrhoeae is significantly suppressed by the stable G4 scaffold. It is likely that some of the genomic instability associated with G4 may be related to the blockage of human intrinsic methyl-independent MMR attempting to operate near G4 structures.

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Pavlova G. V. et al. G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions // Biomedicines. 2022. Vol. 10. No. 8. p. 1871.
GOST all authors (up to 50) Copy
Pavlova G. V., Savitskaya V. Yu., Dolinnaya N., Monakhova M. V., Litvinova A. V., KUBAREVA E. A., Zvereva M. G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions // Biomedicines. 2022. Vol. 10. No. 8. p. 1871.
RIS |
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RIS Copy
TY - JOUR
DO - 10.3390/biomedicines10081871
UR - https://doi.org/10.3390%2Fbiomedicines10081871
TI - G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions
T2 - Biomedicines
AU - Savitskaya, Victoria Yu
AU - Litvinova, Anastasia V
AU - KUBAREVA, ELENA A.
AU - Pavlova, G V
AU - Dolinnaya, Nina
AU - Monakhova, Mayya V
AU - Zvereva, Maria
PY - 2022
DA - 2022/08/03 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 1871
IS - 8
VL - 10
PMID - 36009419
SN - 2227-9059
ER -
BibTex |
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BibTex Copy
@article{2022_Pavlova
author = {Victoria Yu Savitskaya and Anastasia V Litvinova and ELENA A. KUBAREVA and G V Pavlova and Nina Dolinnaya and Mayya V Monakhova and Maria Zvereva},
title = {G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions},
journal = {Biomedicines},
year = {2022},
volume = {10},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {aug},
url = {https://doi.org/10.3390%2Fbiomedicines10081871},
number = {8},
pages = {1871},
doi = {10.3390/biomedicines10081871}
}
MLA
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MLA Copy
Pavlova, G. V., et al. “G-Quadruplex Formed by the Promoter Region of the hTERT Gene: Structure-Driven Effects on DNA Mismatch Repair Functions.” Biomedicines, vol. 10, no. 8, Aug. 2022, p. 1871. https://doi.org/10.3390%2Fbiomedicines10081871.
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