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Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity

DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and...

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Autores principales: Burgess, Joshua T, Cheong, Chee Man, Suraweera, Amila, Sobanski, Thais, Beard, Sam, Dave, Keyur, Rose, Maddison, Boucher, Didier, Croft, Laura V, Adams, Mark N, O’Byrne, Kenneth, Richard, Derek J, Bolderson, Emma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034644/
https://www.ncbi.nlm.nih.gov/pubmed/33660778
http://dx.doi.org/10.1093/nar/gkab110
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author Burgess, Joshua T
Cheong, Chee Man
Suraweera, Amila
Sobanski, Thais
Beard, Sam
Dave, Keyur
Rose, Maddison
Boucher, Didier
Croft, Laura V
Adams, Mark N
O’Byrne, Kenneth
Richard, Derek J
Bolderson, Emma
author_facet Burgess, Joshua T
Cheong, Chee Man
Suraweera, Amila
Sobanski, Thais
Beard, Sam
Dave, Keyur
Rose, Maddison
Boucher, Didier
Croft, Laura V
Adams, Mark N
O’Byrne, Kenneth
Richard, Derek J
Bolderson, Emma
author_sort Burgess, Joshua T
collection PubMed
description DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and mutations in Banf1 are associated with the severe premature aging syndrome, Néstor–Guillermo Progeria Syndrome. We have previously shown that Banf1 directly regulates the activity of PARP1 in the repair of oxidative DNA lesions. Here, we show that Banf1 also has a role in modulating DNA double-strand break repair through regulation of the DNA-dependent Protein Kinase catalytic subunit, DNA-PKcs. Specifically, we demonstrate that Banf1 relocalizes from the nuclear envelope to sites of DNA double-strand breaks. We also show that Banf1 can bind to and directly inhibit the activity of DNA-PKcs. Supporting this, cellular depletion of Banf1 leads to an increase in non-homologous end-joining and a decrease in homologous recombination, which our data suggest is likely due to unrestrained DNA-PKcs activity. Overall, this study identifies how Banf1 regulates double-strand break repair pathway choice by modulating DNA-PKcs activity to control genome stability within the cell.
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spelling pubmed-80346442021-04-14 Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity Burgess, Joshua T Cheong, Chee Man Suraweera, Amila Sobanski, Thais Beard, Sam Dave, Keyur Rose, Maddison Boucher, Didier Croft, Laura V Adams, Mark N O’Byrne, Kenneth Richard, Derek J Bolderson, Emma Nucleic Acids Res Genome Integrity, Repair and Replication DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and mutations in Banf1 are associated with the severe premature aging syndrome, Néstor–Guillermo Progeria Syndrome. We have previously shown that Banf1 directly regulates the activity of PARP1 in the repair of oxidative DNA lesions. Here, we show that Banf1 also has a role in modulating DNA double-strand break repair through regulation of the DNA-dependent Protein Kinase catalytic subunit, DNA-PKcs. Specifically, we demonstrate that Banf1 relocalizes from the nuclear envelope to sites of DNA double-strand breaks. We also show that Banf1 can bind to and directly inhibit the activity of DNA-PKcs. Supporting this, cellular depletion of Banf1 leads to an increase in non-homologous end-joining and a decrease in homologous recombination, which our data suggest is likely due to unrestrained DNA-PKcs activity. Overall, this study identifies how Banf1 regulates double-strand break repair pathway choice by modulating DNA-PKcs activity to control genome stability within the cell. Oxford University Press 2021-02-28 /pmc/articles/PMC8034644/ /pubmed/33660778 http://dx.doi.org/10.1093/nar/gkab110 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Burgess, Joshua T
Cheong, Chee Man
Suraweera, Amila
Sobanski, Thais
Beard, Sam
Dave, Keyur
Rose, Maddison
Boucher, Didier
Croft, Laura V
Adams, Mark N
O’Byrne, Kenneth
Richard, Derek J
Bolderson, Emma
Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title_full Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title_fullStr Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title_full_unstemmed Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title_short Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
title_sort barrier-to-autointegration-factor (banf1) modulates dna double-strand break repair pathway choice via regulation of dna-dependent kinase (dna-pk) activity
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034644/
https://www.ncbi.nlm.nih.gov/pubmed/33660778
http://dx.doi.org/10.1093/nar/gkab110
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