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Cloning, localization and focus formation at DNA damage sites of canine XRCC4
Various chemotherapies and radiation therapies are useful for killing cancer cells mainly by inducing DNA double-strand breaks (DSBs). Uncovering the molecular mechanisms of DSB repair processes is crucial for developing next-generation radiotherapies and chemotherapeutics for human and animal cance...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Japanese Society of Veterinary Science
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240766/ https://www.ncbi.nlm.nih.gov/pubmed/27644316 http://dx.doi.org/10.1292/jvms.16-0381 |
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author | KOIKE, Manabu YUTOKU, Yasutomo KOIKE, Aki |
author_facet | KOIKE, Manabu YUTOKU, Yasutomo KOIKE, Aki |
author_sort | KOIKE, Manabu |
collection | PubMed |
description | Various chemotherapies and radiation therapies are useful for killing cancer cells mainly by inducing DNA double-strand breaks (DSBs). Uncovering the molecular mechanisms of DSB repair processes is crucial for developing next-generation radiotherapies and chemotherapeutics for human and animal cancers. XRCC4 plays a critical role in Ku-dependent nonhomologous DNA-end joining (NHEJ) in human cells, and is one of the core NHEJ factors. The localization of core NHEJ factors, such as human Ku70 and Ku80, might play a crucial role in regulating NHEJ activity. Recently, companion animals, such as canines, have been proposed to be a good model in many aspects of cancer research. However, the localization and regulation mechanisms of core NHEJ factors in canine cells have not been elucidated. Here, we show that the expression and subcellular localization of canine XRCC4 changes dynamically during the cell cycle. Furthermore, EYFP-canine XRCC4 accumulates quickly at laser-microirradiated DSB sites. The structure of a putative human XRCC4 nuclear localization signal (NLS) is highly conserved in canine, chimpanzee and mouse XRCC4. However, the amino acid residue corresponding to the human XRCC4 K210, thought to be important for nuclear localization, is not conserved in canine XRCC4. Our findings might be useful for the study of the molecular mechanisms of Ku-dependent NHEJ in canine cells and the development of new radiosensitizers that target XRCC4. |
format | Online Article Text |
id | pubmed-5240766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Japanese Society of Veterinary Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52407662017-01-30 Cloning, localization and focus formation at DNA damage sites of canine XRCC4 KOIKE, Manabu YUTOKU, Yasutomo KOIKE, Aki J Vet Med Sci Biochemistry Various chemotherapies and radiation therapies are useful for killing cancer cells mainly by inducing DNA double-strand breaks (DSBs). Uncovering the molecular mechanisms of DSB repair processes is crucial for developing next-generation radiotherapies and chemotherapeutics for human and animal cancers. XRCC4 plays a critical role in Ku-dependent nonhomologous DNA-end joining (NHEJ) in human cells, and is one of the core NHEJ factors. The localization of core NHEJ factors, such as human Ku70 and Ku80, might play a crucial role in regulating NHEJ activity. Recently, companion animals, such as canines, have been proposed to be a good model in many aspects of cancer research. However, the localization and regulation mechanisms of core NHEJ factors in canine cells have not been elucidated. Here, we show that the expression and subcellular localization of canine XRCC4 changes dynamically during the cell cycle. Furthermore, EYFP-canine XRCC4 accumulates quickly at laser-microirradiated DSB sites. The structure of a putative human XRCC4 nuclear localization signal (NLS) is highly conserved in canine, chimpanzee and mouse XRCC4. However, the amino acid residue corresponding to the human XRCC4 K210, thought to be important for nuclear localization, is not conserved in canine XRCC4. Our findings might be useful for the study of the molecular mechanisms of Ku-dependent NHEJ in canine cells and the development of new radiosensitizers that target XRCC4. The Japanese Society of Veterinary Science 2016-09-18 2016-12 /pmc/articles/PMC5240766/ /pubmed/27644316 http://dx.doi.org/10.1292/jvms.16-0381 Text en ©2016 The Japanese Society of Veterinary Science http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
spellingShingle | Biochemistry KOIKE, Manabu YUTOKU, Yasutomo KOIKE, Aki Cloning, localization and focus formation at DNA damage sites of canine XRCC4 |
title | Cloning, localization and focus formation at DNA damage sites of canine
XRCC4 |
title_full | Cloning, localization and focus formation at DNA damage sites of canine
XRCC4 |
title_fullStr | Cloning, localization and focus formation at DNA damage sites of canine
XRCC4 |
title_full_unstemmed | Cloning, localization and focus formation at DNA damage sites of canine
XRCC4 |
title_short | Cloning, localization and focus formation at DNA damage sites of canine
XRCC4 |
title_sort | cloning, localization and focus formation at dna damage sites of canine
xrcc4 |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240766/ https://www.ncbi.nlm.nih.gov/pubmed/27644316 http://dx.doi.org/10.1292/jvms.16-0381 |
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