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Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage

Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anapha...

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Autores principales: Kim, Ju Hwan, Kim, Hak Rim, Patel, Rajnikant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129849/
https://www.ncbi.nlm.nih.gov/pubmed/36642928
http://dx.doi.org/10.4062/biomolther.2022.130
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author Kim, Ju Hwan
Kim, Hak Rim
Patel, Rajnikant
author_facet Kim, Ju Hwan
Kim, Hak Rim
Patel, Rajnikant
author_sort Kim, Ju Hwan
collection PubMed
description Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.
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spelling pubmed-101298492023-04-27 Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage Kim, Ju Hwan Kim, Hak Rim Patel, Rajnikant Biomol Ther (Seoul) Original Article Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response. The Korean Society of Applied Pharmacology 2023-05-01 2023-01-16 /pmc/articles/PMC10129849/ /pubmed/36642928 http://dx.doi.org/10.4062/biomolther.2022.130 Text en Copyright © 2023, The Korean Society of Applied Pharmacology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Ju Hwan
Kim, Hak Rim
Patel, Rajnikant
Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title_full Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title_fullStr Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title_full_unstemmed Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title_short Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
title_sort inactivation of mad2b enhances apoptosis in human cervical cancer cell line upon cisplatin-induced dna damage
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129849/
https://www.ncbi.nlm.nih.gov/pubmed/36642928
http://dx.doi.org/10.4062/biomolther.2022.130
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