Abasic Site–Peptide Cross-Links are Blocking Lesions Repaired by AP Endonucleases | Sciact - CRIS-система Института катализа

Abasic Site–Peptide Cross-Links are Blocking Lesions Repaired by AP Endonucleases Научная публикация

Журнал

Nucleic Acids Research
ISSN: 0305-1048 , E-ISSN: 1362-4962

Вых. Данные

Год: 2023, Том: 51, Номер: 12, Страницы: 6321-6336 Страниц : 16 DOI: 10.1093/nar/gkad423

Авторы

Yudkina Anna V. ^1,2 , Bulgakov Nikita A. ¹ , Kim Daria V. ^1,2 , Baranova Svetlana V. ¹ , Ishchenko Alexander A. ³ , Saparbaev Murat K. ³ , Koval Vladimir V. ¹ , Zharkov Dmitry O. ^1,2

Организации

1	SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia
2	Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
3	Groupe “Mechanisms of DNA Repair and Carcinogenesis”, Equipe Labellisee´ LIGUE 2016, CNRS UMR9019, Universite´ Paris-Saclay, Gustave Roussy Cancer Campus, F-94805 Villejuif, France

Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from spontaneous hydrolysis of the N-glycosidic bond and as base excision repair (BER) intermediates. AP sites and their derivatives readily trap DNA-bound proteins, resulting in DNA–protein cross-links. Those are subject to proteolysis but the fate of the resulting AP–peptide cross-links (APPXLs) is unclear. Here, we report two in vitro models of APPXLs synthesized by cross-linking of DNA glycosylases Fpg and OGG1 to DNA followed by trypsinolysis. The reaction with Fpg produces a 10-mer peptide cross-linked through its N-terminus, while OGG1 yields a 23-mer peptide attached through an internal lysine. Both adducts strongly blocked Klenow fragment, phage RB69 polymerase, Saccharolobus solfataricus Dpo4, and African swine fever virus PolX. In the residual lesion bypass, mostly dAMP and dGMP were incorporated by Klenow and RB69 polymerases, while Dpo4 and PolX used primer/template misalignment. Of AP endonucleases involved in BER, Escherichia coli endonuclease IV and its yeast homolog Apn1p efficiently hydrolyzed both adducts. In contrast, E. coli exonuclease III and human APE1 showed little activity on APPXL substrates. Our data suggest that APPXLs produced by proteolysis of AP site-trapped proteins may be removed by the BER pathway, at least in bacterial and yeast cells.

Yudkina A. , Bulgakov N. , Kim D. , Baranova S. , Ishchenko A. , Saparbaev M. , Koval V. , Zharkov D.
Abasic Site–Peptide Cross-Links are Blocking Lesions Repaired by AP Endonucleases
Nucleic Acids Research. 2023. V.51. N12. P.6321-6336. DOI: 10.1093/nar/gkad423 WOS Scopus CAPlusCA PMID OpenAlex

Поступила в редакцию:	20 дек. 2022 г.
Принята к публикации:	15 мая 2023 г.
Опубликована online:	22 мая 2023 г.
Опубликована в печати:	7 июл. 2023 г.

Web of science:	WOS:000992141900001
Scopus:	2-s2.0-85164936476
Chemical Abstracts:	2023:2307927
Chemical Abstracts (print):	185:2572
PMID (PubMed):	37216593
OpenAlex:	W4377289946

БД	Цитирований
OpenAlex	6
Web of science	8
Scopus	8