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Regulation of Chk1

Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collab...

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Autores principales: Tapia-Alveal, Claudia, Calonge, Teresa M, O'Connell, Matthew J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685127/
https://www.ncbi.nlm.nih.gov/pubmed/19400965
http://dx.doi.org/10.1186/1747-1028-4-8
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author Tapia-Alveal, Claudia
Calonge, Teresa M
O'Connell, Matthew J
author_facet Tapia-Alveal, Claudia
Calonge, Teresa M
O'Connell, Matthew J
author_sort Tapia-Alveal, Claudia
collection PubMed
description Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collaborate to activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation requires the phosphorylation of residues in the C-terminal domain, and this is catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal regulatory domain activates the N-terminal kinase domain has not been elucidated, though some studies have suggested that this phosphorylation relieves an inhibitory intramolecular interaction between the N- and C-termini. However, recent studies in the fission yeast Schizosaccharomyces pombe have revealed that there is more to Chk1 regulation than this auto-inhibition model, and we review these findings and their implication to the biology of this genome integrity determinant.
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spelling pubmed-26851272009-05-22 Regulation of Chk1 Tapia-Alveal, Claudia Calonge, Teresa M O'Connell, Matthew J Cell Div Review Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collaborate to activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation requires the phosphorylation of residues in the C-terminal domain, and this is catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal regulatory domain activates the N-terminal kinase domain has not been elucidated, though some studies have suggested that this phosphorylation relieves an inhibitory intramolecular interaction between the N- and C-termini. However, recent studies in the fission yeast Schizosaccharomyces pombe have revealed that there is more to Chk1 regulation than this auto-inhibition model, and we review these findings and their implication to the biology of this genome integrity determinant. BioMed Central 2009-04-29 /pmc/articles/PMC2685127/ /pubmed/19400965 http://dx.doi.org/10.1186/1747-1028-4-8 Text en Copyright © 2009 Tapia-Alveal et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Tapia-Alveal, Claudia
Calonge, Teresa M
O'Connell, Matthew J
Regulation of Chk1
title Regulation of Chk1
title_full Regulation of Chk1
title_fullStr Regulation of Chk1
title_full_unstemmed Regulation of Chk1
title_short Regulation of Chk1
title_sort regulation of chk1
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685127/
https://www.ncbi.nlm.nih.gov/pubmed/19400965
http://dx.doi.org/10.1186/1747-1028-4-8
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