Open Access
International Journal of Molecular Sciences, volume 23, issue 4, pages 2212
A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase
Publication type: Journal Article
Publication date: 2022-02-17
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 16616596, 14220067
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract
Human NEIL2 DNA glycosylase (hNEIL2) is a base excision repair protein that removes oxidative lesions from DNA. A distinctive feature of hNEIL2 is its preference for the lesions in bubbles and other non-canonical DNA structures. Although a number of associations of polymorphisms in the hNEIL2 gene were reported, there is little data on the functionality of the encoded protein variants, as follows: only hNEIL2 R103Q was described as unaffected, and R257L, as less proficient in supporting the repair in a reconstituted system. Here, we report the biochemical characterization of two hNEIL2 variants found as polymorphisms in the general population, R103W and P304T. Arg103 is located in a long disordered segment within the N-terminal domain of hNEIL2, while Pro304 occupies a position in the β-turn of the DNA-binding zinc finger motif. Similar to the wild-type protein, both of the variants could catalyze base excision and nick DNA by β-elimination but demonstrated a lower affinity for DNA. Steady-state kinetics indicates that the P304T variant has its catalytic efficiency (in terms of kcat/KM) reduced ~5-fold compared with the wild-type hNEIL2, whereas the R103W enzyme is much less affected. The P304T variant was also less proficient than the wild-type, or R103W hNEIL2, in the removal of damaged bases from single-stranded and bubble-containing DNA. Overall, hNEIL2 P304T could be worthy of a detailed epidemiological analysis as a possible cancer risk modifier.
Citations by journals
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International Journal of Molecular Sciences
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International Journal of Molecular Sciences
2 publications, 33.33%
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Biochimie
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1 publication, 16.67%
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Nucleic Acids Research
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1 publication, 16.67%
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Environmental and Molecular Mutagenesis
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Citations by publishers
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2
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
2 publications, 33.33%
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Elsevier
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Elsevier
1 publication, 16.67%
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Oxford University Press
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Oxford University Press
1 publication, 16.67%
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Wiley
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Wiley
1 publication, 16.67%
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Research Square Platform LLC
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Research Square Platform LLC, 1, 16.67%
Research Square Platform LLC
1 publication, 16.67%
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2
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Kakhkharova Z. I. et al. A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase // International Journal of Molecular Sciences. 2022. Vol. 23. No. 4. p. 2212.
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Kakhkharova Z. I., Zharkov D. O., Grin I. R. A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase // International Journal of Molecular Sciences. 2022. Vol. 23. No. 4. p. 2212.
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TY - JOUR
DO - 10.3390/ijms23042212
UR - https://doi.org/10.3390%2Fijms23042212
TI - A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase
T2 - International Journal of Molecular Sciences
AU - Kakhkharova, Zarina I
AU - Grin, Inga R
AU - Zharkov, Dmitry O
PY - 2022
DA - 2022/02/17 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 2212
IS - 4
VL - 23
SN - 1661-6596
SN - 1422-0067
ER -
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@article{2022_Kakhkharova,
author = {Zarina I Kakhkharova and Inga R Grin and Dmitry O Zharkov},
title = {A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase},
journal = {International Journal of Molecular Sciences},
year = {2022},
volume = {23},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {feb},
url = {https://doi.org/10.3390%2Fijms23042212},
number = {4},
pages = {2212},
doi = {10.3390/ijms23042212}
}
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MLA
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Kakhkharova, Zarina I., et al. “A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase.” International Journal of Molecular Sciences, vol. 23, no. 4, Feb. 2022, p. 2212. https://doi.org/10.3390%2Fijms23042212.