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BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes

Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression prof...

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Autores principales: Chen, Pei, Hu, Huan, Chen, Zhao, Cai, Xiaoxiao, Zhang, Zhang, Yang, Ying, Yu, Na, Zhang, Jing, Xia, Lei, Ge, Jian, Yu, Keming, Zhuang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053421/
https://www.ncbi.nlm.nih.gov/pubmed/24919198
http://dx.doi.org/10.1371/journal.pone.0099371
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author Chen, Pei
Hu, Huan
Chen, Zhao
Cai, Xiaoxiao
Zhang, Zhang
Yang, Ying
Yu, Na
Zhang, Jing
Xia, Lei
Ge, Jian
Yu, Keming
Zhuang, Jing
author_facet Chen, Pei
Hu, Huan
Chen, Zhao
Cai, Xiaoxiao
Zhang, Zhang
Yang, Ying
Yu, Na
Zhang, Jing
Xia, Lei
Ge, Jian
Yu, Keming
Zhuang, Jing
author_sort Chen, Pei
collection PubMed
description Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes.
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spelling pubmed-40534212014-06-18 BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes Chen, Pei Hu, Huan Chen, Zhao Cai, Xiaoxiao Zhang, Zhang Yang, Ying Yu, Na Zhang, Jing Xia, Lei Ge, Jian Yu, Keming Zhuang, Jing PLoS One Research Article Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes. Public Library of Science 2014-06-11 /pmc/articles/PMC4053421/ /pubmed/24919198 http://dx.doi.org/10.1371/journal.pone.0099371 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Chen, Pei
Hu, Huan
Chen, Zhao
Cai, Xiaoxiao
Zhang, Zhang
Yang, Ying
Yu, Na
Zhang, Jing
Xia, Lei
Ge, Jian
Yu, Keming
Zhuang, Jing
BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title_full BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title_fullStr BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title_full_unstemmed BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title_short BRCA1 Silencing Is Associated with Failure of DNA Repairing in Retinal Neurocytes
title_sort brca1 silencing is associated with failure of dna repairing in retinal neurocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053421/
https://www.ncbi.nlm.nih.gov/pubmed/24919198
http://dx.doi.org/10.1371/journal.pone.0099371
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