Bypass of Abasic Site–Peptide Cross-Links by Human Repair and Translesion DNA Polymerases | Sciact - CRIS-system of Boreskov Institute of Catalysis

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

Journal

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

Output data

Year: 2023, Volume: 24, Number: 13, Article number : 10877, Pages count : 22 DOI: 10.3390/ijms241310877

Tags

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

Authors

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

Affiliations

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 ANCAN PMID OpenAlex

Submitted:	Apr 30, 2023
Accepted:	Jun 27, 2023
Published online:	Jun 29, 2023
Published print:	Jul 1, 2023

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

DB	Citing
OpenAlex	2
Web of science	3
Scopus	3