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Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1
TopBP1 is a scaffold protein that coordinates activation of the DNA-damage-checkpoint response by coupling binding of the 9-1-1 checkpoint clamp at sites of ssDNA, to activation of the ATR–ATRIP checkpoint kinase complex. We have now determined the crystal structure of the N-terminal region of human...
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017600/ https://www.ncbi.nlm.nih.gov/pubmed/20724438 http://dx.doi.org/10.1093/nar/gkq743 |
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author | Rappas, Mathieu Oliver, Antony W. Pearl, Laurence H. |
author_facet | Rappas, Mathieu Oliver, Antony W. Pearl, Laurence H. |
author_sort | Rappas, Mathieu |
collection | PubMed |
description | TopBP1 is a scaffold protein that coordinates activation of the DNA-damage-checkpoint response by coupling binding of the 9-1-1 checkpoint clamp at sites of ssDNA, to activation of the ATR–ATRIP checkpoint kinase complex. We have now determined the crystal structure of the N-terminal region of human TopBP1, revealing an unexpected triple-BRCT domain structure. The arrangement of the BRCT domains differs significantly from previously described tandem BRCT domain structures, and presents two distinct sites for binding phosphopeptides in the second and third BRCT domains. We show that the site in the second but not third BRCT domain in the N-terminus of TopBP1, provides specific interaction with a phosphorylated motif at pSer387 in Rad9, which can be generated by CK2. |
format | Text |
id | pubmed-3017600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30176002011-01-10 Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 Rappas, Mathieu Oliver, Antony W. Pearl, Laurence H. Nucleic Acids Res Structural Biology TopBP1 is a scaffold protein that coordinates activation of the DNA-damage-checkpoint response by coupling binding of the 9-1-1 checkpoint clamp at sites of ssDNA, to activation of the ATR–ATRIP checkpoint kinase complex. We have now determined the crystal structure of the N-terminal region of human TopBP1, revealing an unexpected triple-BRCT domain structure. The arrangement of the BRCT domains differs significantly from previously described tandem BRCT domain structures, and presents two distinct sites for binding phosphopeptides in the second and third BRCT domains. We show that the site in the second but not third BRCT domain in the N-terminus of TopBP1, provides specific interaction with a phosphorylated motif at pSer387 in Rad9, which can be generated by CK2. Oxford University Press 2011-01 2010-08-19 /pmc/articles/PMC3017600/ /pubmed/20724438 http://dx.doi.org/10.1093/nar/gkq743 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Rappas, Mathieu Oliver, Antony W. Pearl, Laurence H. Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title | Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title_full | Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title_fullStr | Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title_full_unstemmed | Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title_short | Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1 |
title_sort | structure and function of the rad9-binding region of the dna-damage checkpoint adaptor topbp1 |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017600/ https://www.ncbi.nlm.nih.gov/pubmed/20724438 http://dx.doi.org/10.1093/nar/gkq743 |
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