Stalling of Eukaryotic Translesion DNA Polymerases at DNA-Protein Cross-Links | Sciact - CRIS-system of Boreskov Institute of Catalysis

Stalling of Eukaryotic Translesion DNA Polymerases at DNA-Protein Cross-Links Full article

Journal

Genes
ISSN: 2073-4425

Output data

Year: 2022, Volume: 13, Number: 2, Article number : 166, Pages count : 15 DOI: 10.3390/genes13020166

Tags

DNA–protein cross-link; DNA polymerases; DNA replication; translesion synthesis

Authors

Yudkina Anna V. ¹ , Shilkin Evgeniy S. ² , Makarova Alena V. ² , Zharkov Dmitry O. ^3,1

Affiliations

1	Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia
2	Institute of Molecular Genetics, National Research Center «Kurchatov Institute», 2 Kurchatov sq., 123182 Moscow, Russia
3	Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St., 630090 Novosibirsk, Russia

DNA-protein cross-links (DPCs) are extremely bulky adducts that interfere with replication. In human cells, they are processed by SPRTN, a protease activated by DNA polymerases stuck at DPCs. We have recently proposed the mechanism of the interaction of DNA polymerases with DPCs, involving a clash of protein surfaces followed by the distortion of the cross-linked protein. Here, we used a model DPC, located in the single-stranded template, the template strand of double-stranded DNA, or the displaced strand, to study the eukaryotic translesion DNA polymerases ζ (POLζ), ι (POLι) and η (POLη). POLι demonstrated poor synthesis on the DPC-containing substrates. POLζ and POLη paused at sites dictated by the footprints of the polymerase and the cross-linked protein. Beyond that, POLζ was able to elongate the primer to the cross-link site when a DPC was in the template. Surprisingly, POLη was not only able to reach the cross-link site but also incorporated 1–2 nucleotides past it, which makes POLη the most efficient DNA polymerase on DPC-containing substrates. However, a DPC in the displaced strand was an insurmountable obstacle for all polymerases, which stalled several nucleotides before the cross-link site. Overall, the behavior of translesion polymerases agrees with the model of protein clash and distortion described above.

Yudkina A.V. , Shilkin E.S. , Makarova A.V. , Zharkov D.O.
Stalling of Eukaryotic Translesion DNA Polymerases at DNA-Protein Cross-Links
Genes. 2022. V.13. N2. 166 :1-15. DOI: 10.3390/genes13020166 WOS Scopus РИНЦ AN PMID OpenAlex

Submitted:	Dec 30, 2021
Accepted:	Jan 16, 2022
Published online:	Jan 18, 2022
Published print:	Feb 1, 2022

Web of science:	WOS:000769507400001
Scopus:	2-s2.0-85125349182
Elibrary:	48185597
Chemical Abstracts:	2022:570632
PMID:	35205211
OpenAlex:	W4205931361

DB	Citing
OpenAlex	8
Web of science	9
Scopus	9