Research output: Contribution to journal › Review article › peer-review
Nucleotide excision repair : From molecular defects to neurological abnormalities. / Krasikova, Yuliya; Rechkunova, Nadejda; Lavrik, Olga.
In: International Journal of Molecular Sciences, Vol. 22, No. 12, 6220, 02.06.2021.Research output: Contribution to journal › Review article › peer-review
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TY - JOUR
T1 - Nucleotide excision repair
T2 - From molecular defects to neurological abnormalities
AU - Krasikova, Yuliya
AU - Rechkunova, Nadejda
AU - Lavrik, Olga
N1 - Funding Information: Funding: This study was funded by the Russian Science Foundation, grant number 21-64-00017 (for N.R. and O.L.), and by the Program of Fundamental Scientific Research of the State Academies of Sciences (no. 0245-2021-0009). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Nucleotide excision repair (NER) is the most versatile DNA repair pathway, which can remove diverse bulky DNA lesions destabilizing a DNA duplex. NER defects cause several au-tosomal recessive genetic disorders. Xeroderma pigmentosum (XP) is one of the NER-associated syndromes characterized by low efficiency of the removal of bulky DNA adducts generated by ultraviolet radiation. XP patients have extremely high ultraviolet-light sensitivity of sun-exposed tissues, often resulting in multiple skin and eye cancers. Some XP patients develop characteristic neurodegeneration that is believed to derive from their inability to repair neuronal DNA damaged by endogenous metabolites. A specific class of oxidatively induced DNA lesions, 8,5′-cyclopurine-2′-deoxynucleosides, is considered endogenous DNA lesions mainly responsible for neurological problems in XP. Growing evidence suggests that XP is accompanied by defective mitophagy, as in primary mitochondrial disorders. Moreover, NER pathway is absent in mitochondria, implying that the mitochondrial dysfunction is secondary to nuclear NER defects. In this review, we discuss the current understanding of the NER molecular mechanism and focuses on the NER linkage with the neurological degeneration in patients with XP. We also present recent research advances regard-ing NER involvement in oxidative DNA lesion repair. Finally, we highlight how mitochondrial dysfunction may be associated with XP.
AB - Nucleotide excision repair (NER) is the most versatile DNA repair pathway, which can remove diverse bulky DNA lesions destabilizing a DNA duplex. NER defects cause several au-tosomal recessive genetic disorders. Xeroderma pigmentosum (XP) is one of the NER-associated syndromes characterized by low efficiency of the removal of bulky DNA adducts generated by ultraviolet radiation. XP patients have extremely high ultraviolet-light sensitivity of sun-exposed tissues, often resulting in multiple skin and eye cancers. Some XP patients develop characteristic neurodegeneration that is believed to derive from their inability to repair neuronal DNA damaged by endogenous metabolites. A specific class of oxidatively induced DNA lesions, 8,5′-cyclopurine-2′-deoxynucleosides, is considered endogenous DNA lesions mainly responsible for neurological problems in XP. Growing evidence suggests that XP is accompanied by defective mitophagy, as in primary mitochondrial disorders. Moreover, NER pathway is absent in mitochondria, implying that the mitochondrial dysfunction is secondary to nuclear NER defects. In this review, we discuss the current understanding of the NER molecular mechanism and focuses on the NER linkage with the neurological degeneration in patients with XP. We also present recent research advances regard-ing NER involvement in oxidative DNA lesion repair. Finally, we highlight how mitochondrial dysfunction may be associated with XP.
KW - Base excision repair
KW - Mitophagy
KW - Neurodegeneration
KW - Nucleotide excision repair
KW - Oxidative stress
KW - Xeroderma pigmentosum
KW - DNA Repair
KW - Humans
KW - Mitochondria/genetics
KW - Neurodegenerative Diseases/genetics
KW - Ultraviolet Rays/adverse effects
KW - Xeroderma Pigmentosum/genetics
UR - http://www.scopus.com/inward/record.url?scp=85107442906&partnerID=8YFLogxK
U2 - 10.3390/ijms22126220
DO - 10.3390/ijms22126220
M3 - Review article
C2 - 34207557
AN - SCOPUS:85107442906
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 12
M1 - 6220
ER -
ID: 28918654