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ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot
Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the inc...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965082/ https://www.ncbi.nlm.nih.gov/pubmed/21048951 http://dx.doi.org/10.1371/journal.pone.0013554 |
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author | Sun, Jiying Oma, Yukako Harata, Masahiko Kono, Kazuteru Shima, Hiroki Kinomura, Aiko Ikura, Tsuyoshi Suzuki, Hidekazu Mizutani, Shuki Kanaar, Roland Tashiro, Satoshi |
author_facet | Sun, Jiying Oma, Yukako Harata, Masahiko Kono, Kazuteru Shima, Hiroki Kinomura, Aiko Ikura, Tsuyoshi Suzuki, Hidekazu Mizutani, Shuki Kanaar, Roland Tashiro, Satoshi |
author_sort | Sun, Jiying |
collection | PubMed |
description | Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA) and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots. |
format | Text |
id | pubmed-2965082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29650822010-11-03 ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot Sun, Jiying Oma, Yukako Harata, Masahiko Kono, Kazuteru Shima, Hiroki Kinomura, Aiko Ikura, Tsuyoshi Suzuki, Hidekazu Mizutani, Shuki Kanaar, Roland Tashiro, Satoshi PLoS One Research Article Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA) and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots. Public Library of Science 2010-10-27 /pmc/articles/PMC2965082/ /pubmed/21048951 http://dx.doi.org/10.1371/journal.pone.0013554 Text en Sun et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sun, Jiying Oma, Yukako Harata, Masahiko Kono, Kazuteru Shima, Hiroki Kinomura, Aiko Ikura, Tsuyoshi Suzuki, Hidekazu Mizutani, Shuki Kanaar, Roland Tashiro, Satoshi ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title | ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title_full | ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title_fullStr | ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title_full_unstemmed | ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title_short | ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot |
title_sort | atm modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965082/ https://www.ncbi.nlm.nih.gov/pubmed/21048951 http://dx.doi.org/10.1371/journal.pone.0013554 |
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