The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis

BACKGROUND: The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryoti...

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Autores principales: Zhang, Fengxia, Wei, Mingxuan, Chen, Haoran, Ji, Liting, Nie, Yan, Kang, Jungseog
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509598/
https://www.ncbi.nlm.nih.gov/pubmed/36153541
http://dx.doi.org/10.1186/s13008-022-00081-4
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author Zhang, Fengxia
Wei, Mingxuan
Chen, Haoran
Ji, Liting
Nie, Yan
Kang, Jungseog
author_facet Zhang, Fengxia
Wei, Mingxuan
Chen, Haoran
Ji, Liting
Nie, Yan
Kang, Jungseog
author_sort Zhang, Fengxia
collection PubMed
description BACKGROUND: The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryotic cells. It binds to 53BP1 and antagonizes inappropriate homologous recombination for a proper DNA damage response. Interestingly, an early study reported mitotic defects after PTIP inactivation, but it is not clear whether PTIP directly facilitates mitotic processes. RESULTS: Here, we showed that PTIP is essential for the mitotic integrity of HeLa cells. PTIP inactivation increases cell death during mitotic exit, which appears to result from direct mitotic defects. PTIP inactivation did not affect the G2M DNA damage checkpoint during interphase upon etoposide treatment. However, in mitosis, PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death. Furthermore, PTIP localizes to the mitotic centrosome via BRCT domains at the C-terminus. CONCLUSION: This study reveals a novel function of PTIP in maintaining the genomic stability of higher eukaryotes during mitosis. Therefore, its deregulation, which occurs in various tumors, may destabilize the genome by introducing an abnormal DNA damage response, as well as erroneous chromosome segregation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13008-022-00081-4.
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spelling pubmed-95095982022-09-26 The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis Zhang, Fengxia Wei, Mingxuan Chen, Haoran Ji, Liting Nie, Yan Kang, Jungseog Cell Div Brief Report BACKGROUND: The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryotic cells. It binds to 53BP1 and antagonizes inappropriate homologous recombination for a proper DNA damage response. Interestingly, an early study reported mitotic defects after PTIP inactivation, but it is not clear whether PTIP directly facilitates mitotic processes. RESULTS: Here, we showed that PTIP is essential for the mitotic integrity of HeLa cells. PTIP inactivation increases cell death during mitotic exit, which appears to result from direct mitotic defects. PTIP inactivation did not affect the G2M DNA damage checkpoint during interphase upon etoposide treatment. However, in mitosis, PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death. Furthermore, PTIP localizes to the mitotic centrosome via BRCT domains at the C-terminus. CONCLUSION: This study reveals a novel function of PTIP in maintaining the genomic stability of higher eukaryotes during mitosis. Therefore, its deregulation, which occurs in various tumors, may destabilize the genome by introducing an abnormal DNA damage response, as well as erroneous chromosome segregation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13008-022-00081-4. BioMed Central 2022-09-24 /pmc/articles/PMC9509598/ /pubmed/36153541 http://dx.doi.org/10.1186/s13008-022-00081-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Brief Report
Zhang, Fengxia
Wei, Mingxuan
Chen, Haoran
Ji, Liting
Nie, Yan
Kang, Jungseog
The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title_full The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title_fullStr The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title_full_unstemmed The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title_short The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
title_sort genomic stability regulator ptip is required for proper chromosome segregation in mitosis
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509598/
https://www.ncbi.nlm.nih.gov/pubmed/36153541
http://dx.doi.org/10.1186/s13008-022-00081-4
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