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Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo

Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3–6). Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, stro...

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Autores principales: Tchurikov, Nickolai A., Yudkin, Dmitry V., Gorbacheva, Maria A., Kulemzina, Anastasia I., Grischenko, Irina V., Fedoseeva, Daria M., Sosin, Dmitri V., Kravatsky, Yuri V., Kretova, Olga V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861929/
https://www.ncbi.nlm.nih.gov/pubmed/27160357
http://dx.doi.org/10.1038/srep25866
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author Tchurikov, Nickolai A.
Yudkin, Dmitry V.
Gorbacheva, Maria A.
Kulemzina, Anastasia I.
Grischenko, Irina V.
Fedoseeva, Daria M.
Sosin, Dmitri V.
Kravatsky, Yuri V.
Kretova, Olga V.
author_facet Tchurikov, Nickolai A.
Yudkin, Dmitry V.
Gorbacheva, Maria A.
Kulemzina, Anastasia I.
Grischenko, Irina V.
Fedoseeva, Daria M.
Sosin, Dmitri V.
Kravatsky, Yuri V.
Kretova, Olga V.
author_sort Tchurikov, Nickolai A.
collection PubMed
description Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3–6). Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics.
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spelling pubmed-48619292016-05-20 Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo Tchurikov, Nickolai A. Yudkin, Dmitry V. Gorbacheva, Maria A. Kulemzina, Anastasia I. Grischenko, Irina V. Fedoseeva, Daria M. Sosin, Dmitri V. Kravatsky, Yuri V. Kretova, Olga V. Sci Rep Article Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3–6). Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics. Nature Publishing Group 2016-05-10 /pmc/articles/PMC4861929/ /pubmed/27160357 http://dx.doi.org/10.1038/srep25866 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tchurikov, Nickolai A.
Yudkin, Dmitry V.
Gorbacheva, Maria A.
Kulemzina, Anastasia I.
Grischenko, Irina V.
Fedoseeva, Daria M.
Sosin, Dmitri V.
Kravatsky, Yuri V.
Kretova, Olga V.
Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title_full Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title_fullStr Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title_full_unstemmed Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title_short Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
title_sort hot spots of dna double-strand breaks in human rdna units are produced in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861929/
https://www.ncbi.nlm.nih.gov/pubmed/27160357
http://dx.doi.org/10.1038/srep25866
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