Cargando…
Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo
Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon DNA damage, an activation mechanism involving autophosphorylation has been reported to allow ATM to pho...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592823/ https://www.ncbi.nlm.nih.gov/pubmed/19047460 http://dx.doi.org/10.1083/jcb.200805154 |
_version_ | 1782161589433008128 |
---|---|
author | Daniel, Jeremy A. Pellegrini, Manuela Lee, Ji-Hoon Paull, Tanya T. Feigenbaum, Lionel Nussenzweig, André |
author_facet | Daniel, Jeremy A. Pellegrini, Manuela Lee, Ji-Hoon Paull, Tanya T. Feigenbaum, Lionel Nussenzweig, André |
author_sort | Daniel, Jeremy A. |
collection | PubMed |
description | Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon DNA damage, an activation mechanism involving autophosphorylation has been reported to allow ATM to phosphorylate downstream targets important for cell cycle checkpoints and DNA repair. In humans, serine residues 367, 1893, and 1981 have been shown to be autophosphorylation sites that are individually required for ATM activation. To test the physiological importance of these sites, we generated a transgenic mouse model in which all three conserved ATM serine autophosphorylation sites (S367/1899/1987) have been replaced with alanine. In this study, we show that ATM-dependent responses at both cellular and organismal levels are functional in mice that express a triple serine mutant form of ATM as their sole ATM species. These results lend further support to the notion that ATM autophosphorylation correlates with the DNA damage–induced activation of the kinase but is not required for ATM function in vivo. |
format | Text |
id | pubmed-2592823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25928232009-06-01 Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo Daniel, Jeremy A. Pellegrini, Manuela Lee, Ji-Hoon Paull, Tanya T. Feigenbaum, Lionel Nussenzweig, André J Cell Biol Research Articles Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon DNA damage, an activation mechanism involving autophosphorylation has been reported to allow ATM to phosphorylate downstream targets important for cell cycle checkpoints and DNA repair. In humans, serine residues 367, 1893, and 1981 have been shown to be autophosphorylation sites that are individually required for ATM activation. To test the physiological importance of these sites, we generated a transgenic mouse model in which all three conserved ATM serine autophosphorylation sites (S367/1899/1987) have been replaced with alanine. In this study, we show that ATM-dependent responses at both cellular and organismal levels are functional in mice that express a triple serine mutant form of ATM as their sole ATM species. These results lend further support to the notion that ATM autophosphorylation correlates with the DNA damage–induced activation of the kinase but is not required for ATM function in vivo. The Rockefeller University Press 2008-12-01 /pmc/articles/PMC2592823/ /pubmed/19047460 http://dx.doi.org/10.1083/jcb.200805154 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Daniel, Jeremy A. Pellegrini, Manuela Lee, Ji-Hoon Paull, Tanya T. Feigenbaum, Lionel Nussenzweig, André Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title | Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title_full | Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title_fullStr | Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title_full_unstemmed | Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title_short | Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo |
title_sort | multiple autophosphorylation sites are dispensable for murine atm activation in vivo |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592823/ https://www.ncbi.nlm.nih.gov/pubmed/19047460 http://dx.doi.org/10.1083/jcb.200805154 |
work_keys_str_mv | AT danieljeremya multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo AT pellegrinimanuela multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo AT leejihoon multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo AT paulltanyat multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo AT feigenbaumlionel multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo AT nussenzweigandre multipleautophosphorylationsitesaredispensableformurineatmactivationinvivo |