Nucleotide excision repair: From molecular defects to neurological abnormalities

Yuliya Krasikova, Nadejda Rechkunova, Olga Lavrik

Результат исследования: Научные публикации в периодических изданияхобзорная статьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Номер статьи6220
ЖурналInternational Journal of Molecular Sciences
Том22
Номер выпуска12
DOI
СостояниеОпубликовано - 2 июн 2021

Предметные области OECD FOS+WOS

  • 2.04 ХИМИЧЕСКИЕ ТЕХНОЛОГИИ
  • 1.04 ХИМИЧЕСКИЕ НАУКИ
  • 1.06 БИОЛОГИЧЕСКИЕ НАУКИ

Fingerprint

Подробные сведения о темах исследования «Nucleotide excision repair: From molecular defects to neurological abnormalities». Вместе они формируют уникальный семантический отпечаток (fingerprint).

Цитировать