The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.

Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3...

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Autores principales:	Olga Alster, Anna Bielak-Zmijewska, Grazyna Mosieniak, Maria Moreno-Villanueva, Wioleta Dudka-Ruszkowska, Aleksandra Wojtala, Monika Kusio-Kobiałka, Zbigniew Korwek, Alexander Burkle, Katarzyna Piwocka, Jan K Siwicki, Ewa Sikora
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/113bedff0d2a48deac13c1fd2b904068
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spelling	oai:doaj.org-article:113bedff0d2a48deac13c1fd2b9040682021-11-25T06:04:50ZThe role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.1932-620310.1371/journal.pone.0104964https://doaj.org/article/113bedff0d2a48deac13c1fd2b9040682014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119968/?tool=EBIhttps://doaj.org/toc/1932-6203Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5). S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to γ-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs) did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA-damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin-treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence.Olga AlsterAnna Bielak-ZmijewskaGrazyna MosieniakMaria Moreno-VillanuevaWioleta Dudka-RuszkowskaAleksandra WojtalaMonika Kusio-KobiałkaZbigniew KorwekAlexander BurkleKatarzyna PiwockaJan K SiwickiEwa SikoraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104964 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olga Alster Anna Bielak-Zmijewska Grazyna Mosieniak Maria Moreno-Villanueva Wioleta Dudka-Ruszkowska Aleksandra Wojtala Monika Kusio-Kobiałka Zbigniew Korwek Alexander Burkle Katarzyna Piwocka Jan K Siwicki Ewa Sikora The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
description	Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5). S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to γ-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs) did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA-damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin-treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence.
format	article
author	Olga Alster Anna Bielak-Zmijewska Grazyna Mosieniak Maria Moreno-Villanueva Wioleta Dudka-Ruszkowska Aleksandra Wojtala Monika Kusio-Kobiałka Zbigniew Korwek Alexander Burkle Katarzyna Piwocka Jan K Siwicki Ewa Sikora
author_facet	Olga Alster Anna Bielak-Zmijewska Grazyna Mosieniak Maria Moreno-Villanueva Wioleta Dudka-Ruszkowska Aleksandra Wojtala Monika Kusio-Kobiałka Zbigniew Korwek Alexander Burkle Katarzyna Piwocka Jan K Siwicki Ewa Sikora
author_sort	Olga Alster
title	The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
title_short	The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
title_full	The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
title_fullStr	The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
title_full_unstemmed	The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.
title_sort	role of nibrin in doxorubicin-induced apoptosis and cell senescence in nijmegen breakage syndrome patients lymphocytes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/113bedff0d2a48deac13c1fd2b904068
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The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.

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