Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides | Sciact - CRIS-system of Boreskov Institute of Catalysis

Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides Full article

Journal

International Journal of Molecular Sciences
ISSN: 1422-0067 , E-ISSN: 1661-6596

Output data

Year: 2024, Volume: 25, Number: 11, Article number : 6006, Pages count : 19 DOI: 10.3390/ijms25116006

Tags

DNA polymerases; AP endonucleases; DNA glycosylases; DNA repair; translesion synthesis; β-L-nucleotides

Authors

Yudkina Anna V. ^1,2 , Kim Daria V. ¹ , Zharkov Timofey D. ¹ , Zharkov Dmitry O. ^1,2 , Endutkin Anton V. ¹

Affiliations

1	Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia
2	Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St., 630090 Novosibirsk, Russia

The DNA building blocks 2′-deoxynucleotides are enantiomeric, with their natural β-D-configuration dictated by the sugar moiety. Their synthetic β-L-enantiomers (βLdNs) can be used to obtain L-DNA, which, when fully substituted, is resistant to nucleases and is finding use in many biosensing and nanotechnology applications. However, much less is known about the enzymatic recognition and processing of individual βLdNs embedded in D-DNA. Here, we address the template properties of βLdNs for several DNA polymerases and the ability of base excision repair enzymes to remove these modifications from DNA. The Klenow fragment was fully blocked by βLdNs, whereas DNA polymerase κ bypassed them in an error-free manner. Phage RB69 DNA polymerase and DNA polymerase β treated βLdNs as non-instructive but the latter enzyme shifted towards error-free incorporation on a gapped DNA substrate. DNA glycosylases and AP endonucleases did not process βLdNs. DNA glycosylases sensitive to the base opposite their cognate lesions also did not recognize βLdNs as a correct pairing partner. Nevertheless, when placed in a reporter plasmid, pyrimidine βLdNs were resistant to repair in human cells, whereas purine βLdNs appear to be partly repaired. Overall, βLdNs are unique modifications that are mostly non-instructive but have dual non-instructive/instructive properties in special cases.

Yudkina A.V. , Kim D.V. , Zharkov T.D. , Zharkov D.O. , Endutkin A.V.
Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides
International Journal of Molecular Sciences. 2024. V.25. N11. 6006 :1-19. DOI: 10.3390/ijms25116006 WOS Scopus OpenAlex

Submitted:	Apr 25, 2024
Accepted:	May 28, 2024
Published online:	May 30, 2024
Published print:	Jun 1, 2024

Web of science:	WOS:001245473300001
Scopus:	2-s2.0-85195872430
OpenAlex:	W4399172873

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