Enzymatic bypass of G-quadruplex structures containing oxidative lesions

Podbevšek, Peter (avtor), Plavec, Janez (avtor)

The function of many DNA processing enzymes involves sliding along the double helix or individual DNA strands. Stable secondary structures in the form of G-quadruplexes are difficult for such enzymes to bypass. We used a polymerase stop assay to determine which structural features of the human telomeric and the BCL2 promoter G-quadruplexes can stall progression of the Klenow fragment. Primer extension profiles revealed that G-quartets are effective roadblocks for the Klenow fragment, while auxiliary base pairs can be easily bypassed. Furthermore, we utilized 8-oxoguanine to simulate oxidative damage in G-rich regions and determine the effects on enzyme bypass. In rare cases, oxidative lesions reduce the level of G-quadruplex bypass. In general, however, oxidative lesions reduce G-quadruplex stability and facilitate bypassing of such G-rich regions, especially if the lesion persists in unfolding intermediates. Our findings using Klenow fragment can be extrapolated to other G-quadruplex forming sequences and enzymes that utilise a clamp-like structure to slide along DNA and are involved in processes such as gene expression regulation and telomere maintenance.

• Jezik: Angleški jezik
• Ključne besede: biochemistry, DNA, G-quadruplexes, NMR
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 11 str.
• Številčenje: Vol. 53, iss. 1, art. gkae1157
• PID: 20.500.12556/RUL-169767
• UDK: 577
• ISSN pri članku: 1362-4962
• DOI: 10.1093/nar/gkae1157
• COBISS.SI-ID: 222273283
• Datum objave v RUL: 09.06.2025

Gradivo je del revije

• Naslov: Nucleic acids research (Online)
• Skrajšan naslov: Nucleic acids res. online
• Založnik: Oxford University Press, Nucleic Acids Research
• ISSN: 1362-4962
• COBISS.SI-ID: 2172954

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, DNK, g-kvadrupleksi, NMR

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P1-0242
• Naslov: Kemija in struktura bioloških učinkovin