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Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells

We recently reported that homologous chromosomes make contact at the sites of double-strand breaks (DSBs) induced by ionizing radiation (IR) and the restriction endonuclease I-PpoI in G₀/G₁-phase somatic human cells. The contact involves short segments of homologous chromosomes and is centered on a...

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Autores principales: Gandhi, Manoj, Evdokimova, Viktoria N., Cuenco, Karen T., Bakkenist, Christopher J., Nikiforov, Yuri E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594255/
https://www.ncbi.nlm.nih.gov/pubmed/23370393
http://dx.doi.org/10.4161/cc.23754
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author Gandhi, Manoj
Evdokimova, Viktoria N.
Cuenco, Karen T.
Bakkenist, Christopher J.
Nikiforov, Yuri E.
author_facet Gandhi, Manoj
Evdokimova, Viktoria N.
Cuenco, Karen T.
Bakkenist, Christopher J.
Nikiforov, Yuri E.
author_sort Gandhi, Manoj
collection PubMed
description We recently reported that homologous chromosomes make contact at the sites of double-strand breaks (DSBs) induced by ionizing radiation (IR) and the restriction endonuclease I-PpoI in G₀/G₁-phase somatic human cells. The contact involves short segments of homologous chromosomes and is centered on a DSB that occurs in a gene; contact does not occur at a DSB in intergenic DNA. Contact between homologous chromosomes is abrogated by inhibition of transcription and requires the kinase activity of ATM, but not DNA-PK. Here, we report additional insights into the mechanism underlying this novel phenomenon. We identify four patterns of homologous chromosome contact, and show that contact between homologous arms, but not centrosomes, is induced by IR. Significantly, we demonstrate that contact is induced by IR in non-proliferating, G₀-phase human cells derived from tissue explants. Finally, we show that contact between homologous chromosomes is detectable as early as 5 min after IR. These results point to the existence of a mechanism that rapidly localizes homologous chromosome arms at sites of DSBs in genes in G₀-phase human cells.
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spelling pubmed-35942552013-03-22 Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells Gandhi, Manoj Evdokimova, Viktoria N. Cuenco, Karen T. Bakkenist, Christopher J. Nikiforov, Yuri E. Cell Cycle Extra Views We recently reported that homologous chromosomes make contact at the sites of double-strand breaks (DSBs) induced by ionizing radiation (IR) and the restriction endonuclease I-PpoI in G₀/G₁-phase somatic human cells. The contact involves short segments of homologous chromosomes and is centered on a DSB that occurs in a gene; contact does not occur at a DSB in intergenic DNA. Contact between homologous chromosomes is abrogated by inhibition of transcription and requires the kinase activity of ATM, but not DNA-PK. Here, we report additional insights into the mechanism underlying this novel phenomenon. We identify four patterns of homologous chromosome contact, and show that contact between homologous arms, but not centrosomes, is induced by IR. Significantly, we demonstrate that contact is induced by IR in non-proliferating, G₀-phase human cells derived from tissue explants. Finally, we show that contact between homologous chromosomes is detectable as early as 5 min after IR. These results point to the existence of a mechanism that rapidly localizes homologous chromosome arms at sites of DSBs in genes in G₀-phase human cells. Landes Bioscience 2013-02-15 /pmc/articles/PMC3594255/ /pubmed/23370393 http://dx.doi.org/10.4161/cc.23754 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Extra Views
Gandhi, Manoj
Evdokimova, Viktoria N.
Cuenco, Karen T.
Bakkenist, Christopher J.
Nikiforov, Yuri E.
Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title_full Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title_fullStr Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title_full_unstemmed Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title_short Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells
title_sort homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in g₀-phase human cells
topic Extra Views
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594255/
https://www.ncbi.nlm.nih.gov/pubmed/23370393
http://dx.doi.org/10.4161/cc.23754
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