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Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate
DNA polymerase (pol) μ primarily inserts ribonucleotides into a single-nucleotide gapped DNA intermediate, and the ligation step plays a critical role in the joining of noncomplementary DNA ends during nonhomologous end joining (NHEJ) for the repair of double-strand breaks (DSBs) caused by reactive...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976671/ https://www.ncbi.nlm.nih.gov/pubmed/31969622 http://dx.doi.org/10.1038/s41598-020-57886-y |
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author | Çağlayan, Melike |
author_facet | Çağlayan, Melike |
author_sort | Çağlayan, Melike |
collection | PubMed |
description | DNA polymerase (pol) μ primarily inserts ribonucleotides into a single-nucleotide gapped DNA intermediate, and the ligation step plays a critical role in the joining of noncomplementary DNA ends during nonhomologous end joining (NHEJ) for the repair of double-strand breaks (DSBs) caused by reactive oxygen species. Here, we report that the pol μ insertion products of ribonucleotides (rATP or rCTP), instead of deoxyribonucleotides, opposite 8-oxo-2′-deoxyguanosine (8-oxodG) are efficiently ligated and the presence of Mn(2+) stimulates this coupled reaction in vitro. Moreover, our results point to a role of pol μ in mediating ligation during the mutagenic bypass of 8-oxodG, while 3′-preinserted noncanonical base pairs (3′-rA or 3′-rC) on NHEJ repair intermediates compromise the end joining by DNA ligase I or the DNA ligase IV/XRCC4 complex. |
format | Online Article Text |
id | pubmed-6976671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69766712020-01-29 Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate Çağlayan, Melike Sci Rep Article DNA polymerase (pol) μ primarily inserts ribonucleotides into a single-nucleotide gapped DNA intermediate, and the ligation step plays a critical role in the joining of noncomplementary DNA ends during nonhomologous end joining (NHEJ) for the repair of double-strand breaks (DSBs) caused by reactive oxygen species. Here, we report that the pol μ insertion products of ribonucleotides (rATP or rCTP), instead of deoxyribonucleotides, opposite 8-oxo-2′-deoxyguanosine (8-oxodG) are efficiently ligated and the presence of Mn(2+) stimulates this coupled reaction in vitro. Moreover, our results point to a role of pol μ in mediating ligation during the mutagenic bypass of 8-oxodG, while 3′-preinserted noncanonical base pairs (3′-rA or 3′-rC) on NHEJ repair intermediates compromise the end joining by DNA ligase I or the DNA ligase IV/XRCC4 complex. Nature Publishing Group UK 2020-01-22 /pmc/articles/PMC6976671/ /pubmed/31969622 http://dx.doi.org/10.1038/s41598-020-57886-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Çağlayan, Melike Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title | Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title_full | Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title_fullStr | Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title_full_unstemmed | Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title_short | Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate |
title_sort | pol μ ribonucleotide insertion opposite 8-oxodg facilitates the ligation of premutagenic dna repair intermediate |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976671/ https://www.ncbi.nlm.nih.gov/pubmed/31969622 http://dx.doi.org/10.1038/s41598-020-57886-y |
work_keys_str_mv | AT caglayanmelike polmribonucleotideinsertionopposite8oxodgfacilitatestheligationofpremutagenicdnarepairintermediate |