N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku

The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit,...

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Autores principales: Meek, Katheryn, Lees-Miller, Susan P., Modesti, Mauro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
Genome Integrity, Repair and Replication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326324/
https://www.ncbi.nlm.nih.gov/pubmed/22167471
http://dx.doi.org/10.1093/nar/gkr1211
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author Meek, Katheryn
Lees-Miller, Susan P.
Modesti, Mauro
author_facet Meek, Katheryn
Lees-Miller, Susan P.
Modesti, Mauro
author_sort Meek, Katheryn
collection PubMed
description The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit, Ku) for its activation as a robust nuclear serine/threonine protein kinase. Here, we report the unexpected finding of robust DNA-PKcs activation by N-terminal constraint, independent of either DNA or its regulatory subunit Ku. These data suggest that an N-terminal conformational change (likely induced by DNA binding) induces enzymatic activation.
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spelling pubmed-33263242012-04-16 N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku Meek, Katheryn Lees-Miller, Susan P. Modesti, Mauro Nucleic Acids Res Genome Integrity, Repair and Replication The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit, Ku) for its activation as a robust nuclear serine/threonine protein kinase. Here, we report the unexpected finding of robust DNA-PKcs activation by N-terminal constraint, independent of either DNA or its regulatory subunit Ku. These data suggest that an N-terminal conformational change (likely induced by DNA binding) induces enzymatic activation. Oxford University Press 2012-04 2011-12-13 /pmc/articles/PMC3326324/ /pubmed/22167471 http://dx.doi.org/10.1093/nar/gkr1211 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Meek, Katheryn
Lees-Miller, Susan P.
Modesti, Mauro
N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title_full N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title_fullStr N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title_full_unstemmed N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title_short N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku
title_sort n-terminal constraint activates the catalytic subunit of the dna-dependent protein kinase in the absence of dna or ku
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326324/
https://www.ncbi.nlm.nih.gov/pubmed/22167471
http://dx.doi.org/10.1093/nar/gkr1211
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