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Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2

DEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49–82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DE...

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Autores principales: Özçelik, Emrah, Kalaycı, Ahmet, Çelik, Büşra, Avcı, Açelya, Akyol, Hasan, Kılıç, İrfan Baki, Güzel, Türkan, Çetin, Metin, Öztürk, Merve Tuzlakoğlu, Çalışkaner, Zihni Onur, Tombaz, Melike, Yoleri, Dilan, Konu, Özlen, Kandilci, Ayten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529144/
https://www.ncbi.nlm.nih.gov/pubmed/36190960
http://dx.doi.org/10.1371/journal.pone.0275476
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author Özçelik, Emrah
Kalaycı, Ahmet
Çelik, Büşra
Avcı, Açelya
Akyol, Hasan
Kılıç, İrfan Baki
Güzel, Türkan
Çetin, Metin
Öztürk, Merve Tuzlakoğlu
Çalışkaner, Zihni Onur
Tombaz, Melike
Yoleri, Dilan
Konu, Özlen
Kandilci, Ayten
author_facet Özçelik, Emrah
Kalaycı, Ahmet
Çelik, Büşra
Avcı, Açelya
Akyol, Hasan
Kılıç, İrfan Baki
Güzel, Türkan
Çetin, Metin
Öztürk, Merve Tuzlakoğlu
Çalışkaner, Zihni Onur
Tombaz, Melike
Yoleri, Dilan
Konu, Özlen
Kandilci, Ayten
author_sort Özçelik, Emrah
collection PubMed
description DEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49–82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent γH2AX signal upon doxorubicin treatment, and couldn’t functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms.
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spelling pubmed-95291442022-10-04 Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2 Özçelik, Emrah Kalaycı, Ahmet Çelik, Büşra Avcı, Açelya Akyol, Hasan Kılıç, İrfan Baki Güzel, Türkan Çetin, Metin Öztürk, Merve Tuzlakoğlu Çalışkaner, Zihni Onur Tombaz, Melike Yoleri, Dilan Konu, Özlen Kandilci, Ayten PLoS One Research Article DEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49–82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent γH2AX signal upon doxorubicin treatment, and couldn’t functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms. Public Library of Science 2022-10-03 /pmc/articles/PMC9529144/ /pubmed/36190960 http://dx.doi.org/10.1371/journal.pone.0275476 Text en © 2022 Özçelik et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Özçelik, Emrah
Kalaycı, Ahmet
Çelik, Büşra
Avcı, Açelya
Akyol, Hasan
Kılıç, İrfan Baki
Güzel, Türkan
Çetin, Metin
Öztürk, Merve Tuzlakoğlu
Çalışkaner, Zihni Onur
Tombaz, Melike
Yoleri, Dilan
Konu, Özlen
Kandilci, Ayten
Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title_full Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title_fullStr Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title_full_unstemmed Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title_short Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
title_sort doxorubicin induces prolonged dna damage signal in cells overexpressing dek isoform-2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529144/
https://www.ncbi.nlm.nih.gov/pubmed/36190960
http://dx.doi.org/10.1371/journal.pone.0275476
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