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Displacement of Slow-Turnover DNA Glycosylases by Molecular Traffic on DNA Full article

Journal

Genes
ISSN: 2073-4425

Output data

Year: 2020, Volume: 11, Number: 8, Article number : 866, Pages count : 21 DOI: 10.3390/genes11080866

Tags

DNA damage; DNA repair; tight protein–DNA complexes; DNA polymerases; facilitated diffusion; molecular traffic

Authors

Yudkina Anna V. ^1,2 , Endutkin Anton V. ² , Diatlova Eugenia A. ² , Moor Nina A. ² , Vokhtantsev Ivan P. ^1,2 , Grin Inga R. ^1,2 , Zharkov Dmitry O. ^1,2

Affiliations

1	Siberian Branch of the Russian Acasemy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia
2	Novosibirsk State University, 2 Pirogova St., 630090 Novosibirsk, Russia

In the base excision repair pathway, the initiating enzymes, DNA glycosylases, remove damaged bases and form long-living complexes with the abasic DNA product, but can be displaced by AP endonucleases. However, many nuclear proteins can move along DNA, either actively (such as DNA or RNA polymerases) or by passive one-dimensional diffusion. In most cases, it is not clear whether this movement is disturbed by other bound proteins or how collisions with moving proteins affect the bound proteins, including DNA glycosylases. We have used a two-substrate system to study the displacement of human OGG1 and NEIL1 DNA glycosylases by DNA polymerases in both elongation and diffusion mode and by D4, a passively diffusing subunit of a viral DNA polymerase. The OGG1–DNA product complex was disrupted by DNA polymerase β (POLβ) in both elongation and diffusion mode, Klenow fragment (KF) in the elongation mode and by D4. NEIL1, which has a shorter half-life on DNA, was displaced more efficiently. Hence, both possibly specific interactions with POLβ and nonspecific collisions (KF, D4) can displace DNA glycosylases from DNA. The protein movement along DNA was blocked by very tightly bound Cas9 RNA-targeted nuclease, providing an upper limit on the efficiency of obstacle clearance

Yudkina A.V. , Endutkin A.V. , Diatlova E.A. , Moor N.A. , Vokhtantsev I.P. , Grin I.R. , Zharkov D.O.
Displacement of Slow-Turnover DNA Glycosylases by Molecular Traffic on DNA
Genes. 2020. V.11. N8. 866 :1-21. DOI: 10.3390/genes11080866 WOS Scopus OpenAlex

Submitted:	Jun 24, 2020
Accepted:	Jul 25, 2020
Published print:	Aug 1, 2020
Published online:	Jul 30, 2024

Web of science:	WOS:000577805400001
Scopus:	2-s2.0-85089131803
OpenAlex:	W3045538152

DB	Citing
Web of science	8
OpenAlex	8
Scopus	8