Bypass of Abasic Site–Peptide Cross-Links by Human Repair and Translesion DNA Polymerases | Sciact - CRIS-система Института катализа

Bypass of Abasic Site–Peptide Cross-Links by Human Repair and Translesion DNA Polymerases Научная публикация

Журнал

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

Вых. Данные

Год: 2023, Том: 24, Номер: 13, Номер статьи : 10877, Страниц : 22 DOI: 10.3390/ijms241310877

Ключевые слова

DNA damage; DNA repair; DNA–peptide cross-links; AP sites; DNA polymerases; translesion synthesis; DNA lesion bypass; mutagenesis

Авторы

Yudkina Anna V. ¹ , Barmatov Alexander E. ¹ , Bulgakov Nikita A. ¹ , Boldinova Elizaveta O. ² , Shilkin Evgeniy S. ² , Makarova Alena V. ² , Zharkov Dmitry O. ^3,1

Организации

1	SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia
2	Institute of Molecular Genetics, National Research Center “Kurchatov Institute”, 123182 Moscow, Russia
3	Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia

DNA–protein cross-links remain the least-studied type of DNA damage. Recently, their repair was shown to involve proteolysis; however, the fate of the peptide remnant attached to DNA is unclear. Particularly, peptide cross-links could interfere with DNA polymerases. Apurinuic/apyrimidinic (AP) sites, abundant and spontaneously arising DNA lesions, readily form cross-links with proteins. Their degradation products (AP site–peptide cross-links, APPXLs) are non-instructive and should be even more problematic for polymerases. Here, we address the ability of human DNA polymerases involved in DNA repair and translesion synthesis (POLβ, POLλ, POLη, POLκ and PrimPOL) to carry out synthesis on templates containing AP sites cross-linked to the N-terminus of a 10-mer peptide (APPXL-I) or to an internal lysine of a 23-mer peptide (APPXL-Y). Generally, APPXLs strongly blocked processive DNA synthesis. The blocking properties of APPXL-I were comparable with those of an AP site, while APPXL-Y constituted a much stronger obstruction. POLη and POLκ demonstrated the highest bypass ability. DNA polymerases mostly used dNTP-stabilized template misalignment to incorporate nucleotides when encountering an APPXL. We conclude that APPXLs are likely highly cytotoxic and mutagenic intermediates of AP site–protein cross-link repair and must be quickly eliminated before replication.

Yudkina A.V. , Barmatov A.E. , Bulgakov N.A. , Boldinova E.O. , Shilkin E.S. , Makarova A.V. , Zharkov D.O.
Bypass of Abasic Site–Peptide Cross-Links by Human Repair and Translesion DNA Polymerases
International Journal of Molecular Sciences. 2023. V.24. N13. 10877 :1-22. DOI: 10.3390/ijms241310877 WOS Scopus CAPlusCA PMID OpenAlex

Поступила в редакцию:	30 апр. 2023 г.
Принята к публикации:	27 июн. 2023 г.
Опубликована online:	29 июн. 2023 г.
Опубликована в печати:	1 июл. 2023 г.

Web of science:	WOS:001028392200001
Scopus:	2-s2.0-85164845893
Chemical Abstracts:	2023:1515194
Chemical Abstracts (print):	183:346568
PMID (PubMed):	37446048
OpenAlex:	W4382862375

БД	Цитирований
OpenAlex	2
Web of science	3
Scopus	3