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The role of nucleotide opening dynamics in facilitated target search by DNA-repair proteins.

Authors :
Mishra SK
Sangeeta
Heermann DW
Bhattacherjee A
Source :
Biochimica et biophysica acta. Gene regulatory mechanisms [Biochim Biophys Acta Gene Regul Mech] 2024 Jun; Vol. 1867 (2), pp. 195026. Date of Electronic Publication: 2024 Apr 17.
Publication Year :
2024

Abstract

Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles. Our findings reveal that the dynamics of a non-canonical base generate an entropic signal that guides the one-dimensional search of a repair protein, thereby facilitating the recognition of the lesion site. The width of the funnel perfectly aligns with the one-dimensional diffusion length of DNA-binding proteins. The generic mechanism provides a physical basis for rapid recognition and specificity of DNA damage sensing and recognition.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal interests that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1876-4320
Volume :
1867
Issue :
2
Database :
MEDLINE
Journal :
Biochimica et biophysica acta. Gene regulatory mechanisms
Publication Type :
Academic Journal
Accession number :
38641240
Full Text :
https://doi.org/10.1016/j.bbagrm.2024.195026