Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.

In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid tumors or myeloproliferative disorders, the product of the normal allele is supposed to be functionally impaired or absent. To address the consequence of the loss of CCDC6 expression, we applied lentiviral shRNA in several c...

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Autores principales:	Angeliki Thanasopoulou, Dimitrios J Stravopodis, Konstantinos S Dimas, Juerg Schwaller, Ema Anastasiadou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b3e5a2e594c416390d5cf13f0f483a5
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spelling	oai:doaj.org-article:7b3e5a2e594c416390d5cf13f0f483a52021-11-18T07:27:42ZLoss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.1932-620310.1371/journal.pone.0031007https://doaj.org/article/7b3e5a2e594c416390d5cf13f0f483a52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22363533/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid tumors or myeloproliferative disorders, the product of the normal allele is supposed to be functionally impaired or absent. To address the consequence of the loss of CCDC6 expression, we applied lentiviral shRNA in several cell lines. Loss of CCDC6 resulted in increased cell death with clear shortening of the S phase transition of the cell cycle. Upon exposure to etoposide, the cells lacking CCDC6 did not achieve S-phase accumulation. In the absence of CCDC6 and in the presence of genotoxic stress, like etoposide treatment or UV irradiation, increased accumulation of DNA damage was observed, as indicated by a significant increase of pH2Ax Ser139. 14-3-3σ, a major cell cycle regulator, was down-regulated in CCDC6 lacking cells, regardless of genotoxic stress. Interestingly, in the absence of CCDC6, the well-known genotoxic stress-induced cytoplasmic sequestration of the S-phase checkpoint CDC25C phosphatase did not occur. These observations suggest that CCDC6 plays a key role in cell cycle control, maintenance of genomic stability and cell survival and provide a rational of how disruption of CCDC6 normal function contributes to malignancy.Angeliki ThanasopoulouDimitrios J StravopodisKonstantinos S DimasJuerg SchwallerEma AnastasiadouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31007 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angeliki Thanasopoulou Dimitrios J Stravopodis Konstantinos S Dimas Juerg Schwaller Ema Anastasiadou Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
description	In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid tumors or myeloproliferative disorders, the product of the normal allele is supposed to be functionally impaired or absent. To address the consequence of the loss of CCDC6 expression, we applied lentiviral shRNA in several cell lines. Loss of CCDC6 resulted in increased cell death with clear shortening of the S phase transition of the cell cycle. Upon exposure to etoposide, the cells lacking CCDC6 did not achieve S-phase accumulation. In the absence of CCDC6 and in the presence of genotoxic stress, like etoposide treatment or UV irradiation, increased accumulation of DNA damage was observed, as indicated by a significant increase of pH2Ax Ser139. 14-3-3σ, a major cell cycle regulator, was down-regulated in CCDC6 lacking cells, regardless of genotoxic stress. Interestingly, in the absence of CCDC6, the well-known genotoxic stress-induced cytoplasmic sequestration of the S-phase checkpoint CDC25C phosphatase did not occur. These observations suggest that CCDC6 plays a key role in cell cycle control, maintenance of genomic stability and cell survival and provide a rational of how disruption of CCDC6 normal function contributes to malignancy.
format	article
author	Angeliki Thanasopoulou Dimitrios J Stravopodis Konstantinos S Dimas Juerg Schwaller Ema Anastasiadou
author_facet	Angeliki Thanasopoulou Dimitrios J Stravopodis Konstantinos S Dimas Juerg Schwaller Ema Anastasiadou
author_sort	Angeliki Thanasopoulou
title	Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
title_short	Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
title_full	Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
title_fullStr	Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
title_full_unstemmed	Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.
title_sort	loss of ccdc6 affects cell cycle through impaired intra-s-phase checkpoint control.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7b3e5a2e594c416390d5cf13f0f483a5
work_keys_str_mv	AT angelikithanasopoulou lossofccdc6affectscellcyclethroughimpairedintrasphasecheckpointcontrol AT dimitriosjstravopodis lossofccdc6affectscellcyclethroughimpairedintrasphasecheckpointcontrol AT konstantinossdimas lossofccdc6affectscellcyclethroughimpairedintrasphasecheckpointcontrol AT juergschwaller lossofccdc6affectscellcyclethroughimpairedintrasphasecheckpointcontrol AT emaanastasiadou lossofccdc6affectscellcyclethroughimpairedintrasphasecheckpointcontrol
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Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.

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