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The Activity of Natural Polymorphic Variants of Human DNA Polymerase β Having an Amino Acid Substitution in the Transferase Domain Научная публикация

Журнал Cells
ISSN: 2073-4409
Вых. Данные Год: 2023, Том: 12, Номер: 9, Номер статьи : 1300, Страниц : DOI: 10.3390/cells12091300
Авторы Kladova O.A. 1 , Tyugashev T.E. 1 , Mikuchina E.S. 1 , Kuznetsov N.A. 1,2 , Novopashina D.S. 1 , Kuznetsova A.A. 1
Организации
1 Institute of Chemical Biology and Fundamental Medicine SB RAS
2 Novosibirsk State University

Информация о финансировании (2)

1 МИНИСТЕРСТВО НАУКИ И ВЫСШЕГО ОБРАЗОВАНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ ПФНИ РФ (2021-2030) 0245-2021-0009
2 Российский научный фонд РНФ_мол_гр №21-74-10103

Реферат: To maintain the integrity of the genome, there is a set of enzymatic systems, one of which is base excision repair (BER), which includes sequential action of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases. Normally, BER works efficiently, but the enzymes themselves (whose primary function is the recognition and removal of damaged bases) are subject to amino acid substitutions owing to natural single-nucleotide polymorphisms (SNPs). One of the enzymes in BER is DNA polymerase β (Polβ), whose function is to fill gaps in DNA with complementary dNMPs. It is known that many SNPs can cause an amino acid substitution in this enzyme and a significant decrease in the enzymatic activity. In this study, the activity of four natural variants of Polβ, containing substitution E154A, G189D, M236T, or R254I in the transferase domain, was analyzed using molecular dynamics simulations and pre-steady-state kinetic analyses. It was shown that all tested substitutions lead to a significant reduction in the ability to form a complex with DNA and with incoming dNTP. The G189D substitution also diminished Polβ catalytic activity. Thus, a decrease in the activity of studied mutant forms may be associated with an increased risk of damage to the genome.
Библиографическая ссылка: Kladova O.A. , Tyugashev T.E. , Mikuchina E.S. , Kuznetsov N.A. , Novopashina D.S. , Kuznetsova A.A.
The Activity of Natural Polymorphic Variants of Human DNA Polymerase β Having an Amino Acid Substitution in the Transferase Domain
Cells. 2023. V.12. N9. 1300 . DOI: 10.3390/cells12091300 WOS Scopus PMID OpenAlex
Даты:
Опубликована в печати: 2 мая 2023 г.
Идентификаторы БД:
Web of science: WOS:000987349400001
Scopus: 2-s2.0-85159212971
PMID (PubMed): 37174699
OpenAlex: W4368377494
Цитирование в БД:
БД Цитирований
OpenAlex 3
Scopus 3
Web of science 3
Альметрики: