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The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates

DNA ligase I and DNA ligase III/XRCC1 complex catalyze the ultimate ligation step following DNA polymerase (pol) β nucleotide insertion during base excision repair (BER). Pol β Asn279 and Arg283 are the critical active site residues for the differentiation of an incoming nucleotide and a template ba...

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Autor principal: Çağlayan, Melike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144901/
https://www.ncbi.nlm.nih.gov/pubmed/32140717
http://dx.doi.org/10.1093/nar/gkaa151
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author Çağlayan, Melike
author_facet Çağlayan, Melike
author_sort Çağlayan, Melike
collection PubMed
description DNA ligase I and DNA ligase III/XRCC1 complex catalyze the ultimate ligation step following DNA polymerase (pol) β nucleotide insertion during base excision repair (BER). Pol β Asn279 and Arg283 are the critical active site residues for the differentiation of an incoming nucleotide and a template base and the N-terminal domain of DNA ligase I mediates its interaction with pol β. Here, we show inefficient ligation of pol β insertion products with mismatched or damaged nucleotides, with the exception of a Watson–Crick-like dGTP insertion opposite T, using BER DNA ligases in vitro. Moreover, pol β N279A and R283A mutants deter the ligation of the promutagenic repair intermediates and the presence of N-terminal domain of DNA ligase I in a coupled reaction governs the channeling of the pol β insertion products. Our results demonstrate that the BER DNA ligases are compromised by subtle changes in all 12 possible noncanonical base pairs at the 3′-end of the nicked repair intermediate. These findings contribute to understanding of how the identity of the mismatch affects the substrate channeling of the repair pathway and the mechanism underlying the coordination between pol β and DNA ligase at the final ligation step to maintain the BER efficiency.
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spelling pubmed-71449012020-04-13 The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates Çağlayan, Melike Nucleic Acids Res Genome Integrity, Repair and Replication DNA ligase I and DNA ligase III/XRCC1 complex catalyze the ultimate ligation step following DNA polymerase (pol) β nucleotide insertion during base excision repair (BER). Pol β Asn279 and Arg283 are the critical active site residues for the differentiation of an incoming nucleotide and a template base and the N-terminal domain of DNA ligase I mediates its interaction with pol β. Here, we show inefficient ligation of pol β insertion products with mismatched or damaged nucleotides, with the exception of a Watson–Crick-like dGTP insertion opposite T, using BER DNA ligases in vitro. Moreover, pol β N279A and R283A mutants deter the ligation of the promutagenic repair intermediates and the presence of N-terminal domain of DNA ligase I in a coupled reaction governs the channeling of the pol β insertion products. Our results demonstrate that the BER DNA ligases are compromised by subtle changes in all 12 possible noncanonical base pairs at the 3′-end of the nicked repair intermediate. These findings contribute to understanding of how the identity of the mismatch affects the substrate channeling of the repair pathway and the mechanism underlying the coordination between pol β and DNA ligase at the final ligation step to maintain the BER efficiency. Oxford University Press 2020-04-17 2020-03-06 /pmc/articles/PMC7144901/ /pubmed/32140717 http://dx.doi.org/10.1093/nar/gkaa151 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Çağlayan, Melike
The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title_full The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title_fullStr The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title_full_unstemmed The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title_short The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates
title_sort ligation of pol β mismatch insertion products governs the formation of promutagenic base excision dna repair intermediates
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144901/
https://www.ncbi.nlm.nih.gov/pubmed/32140717
http://dx.doi.org/10.1093/nar/gkaa151
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