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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... Full description

Journal Title: PloS one 2014, Vol.9(6), p.e99371
Main Author: Chen, Pei
Other Authors: Hu, Huan , Chen, Zhao , Cai, Xiaoxiao , Zhang, Zhang , Yang, Ying , Yu, Na , Zhang, Jing , Xia, Lei , Ge, Jian , Yu, Keming , Zhuang, Jing
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0099371
Link: http://search.proquest.com/docview/1535622575/?pq-origsite=primo
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title: BRCA1 silencing is associated with failure of DNA repairing in retinal neurocytes.
format: Article
creator:
  • Chen, Pei
  • Hu, Huan
  • Chen, Zhao
  • Cai, Xiaoxiao
  • Zhang, Zhang
  • Yang, Ying
  • Yu, Na
  • Zhang, Jing
  • Xia, Lei
  • Ge, Jian
  • Yu, Keming
  • Zhuang, Jing
subjects:
  • Animals–Genetics
  • DNA End-Joining Repair–Metabolism
  • Gene Silencing–Cytology
  • Genes, Brca1–Metabolism
  • Mice–Radiation Effects
  • Neurons–Radiation Effects
  • Retina–Radiation Effects
ispartof: PloS one, 2014, Vol.9(6), p.e99371
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.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0099371
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleBRCA1 silencing is associated with failure of DNA repairing in retinal neurocytes.
creatorChen, Pei ; Hu, Huan ; Chen, Zhao ; Cai, Xiaoxiao ; Zhang, Zhang ; Yang, Ying ; Yu, Na ; Zhang, Jing ; Xia, Lei ; Ge, Jian ; Yu, Keming ; Zhuang, Jing
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identifierE-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0099371
subjectAnimals–Genetics ; DNA End-Joining Repair–Metabolism ; Gene Silencing–Cytology ; Genes, Brca1–Metabolism ; Mice–Radiation Effects ; Neurons–Radiation Effects ; Retina–Radiation Effects
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descriptionRetinal 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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