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TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks

TopBP1 and the Rad9–Rad1–Hus1 (9-1-1) complex activate the ataxia telangiectasia mutated and Rad3-related (ATR) protein kinase at stalled replication forks. ATR is recruited to stalled forks through its binding partner, ATR-interacting protein (ATRIP); however, it is unclear how TopBP1 and 9-1-1 are...

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Detalles Bibliográficos
Autores principales: Yan, Shan, Michael, W. Matthew
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699152/
https://www.ncbi.nlm.nih.gov/pubmed/19289795
http://dx.doi.org/10.1083/jcb.200810185
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author Yan, Shan
Michael, W. Matthew
author_facet Yan, Shan
Michael, W. Matthew
author_sort Yan, Shan
collection PubMed
description TopBP1 and the Rad9–Rad1–Hus1 (9-1-1) complex activate the ataxia telangiectasia mutated and Rad3-related (ATR) protein kinase at stalled replication forks. ATR is recruited to stalled forks through its binding partner, ATR-interacting protein (ATRIP); however, it is unclear how TopBP1 and 9-1-1 are recruited so that they may join ATR–ATRIP and initiate signaling. In this study, we use Xenopus laevis egg extracts to determine the requirements for 9-1-1 loading. We show that TopBP1 is required for the recruitment of both 9-1-1 and DNA polymerase (pol)-α to sites of replication stress. Furthermore, we show that pol-α is also directly required for Rad9 loading. Our study identifies an assembly pathway, which is controlled by TopBP1 and includes pol-α, that mediates the loading of the 9-1-1 complex onto stalled replication forks. These findings clarify early events in the assembly of checkpoint signaling complexes on DNA and identify TopBP1 as a critical sensor of replication stress.
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spelling pubmed-26991522009-09-23 TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks Yan, Shan Michael, W. Matthew J Cell Biol Research Articles TopBP1 and the Rad9–Rad1–Hus1 (9-1-1) complex activate the ataxia telangiectasia mutated and Rad3-related (ATR) protein kinase at stalled replication forks. ATR is recruited to stalled forks through its binding partner, ATR-interacting protein (ATRIP); however, it is unclear how TopBP1 and 9-1-1 are recruited so that they may join ATR–ATRIP and initiate signaling. In this study, we use Xenopus laevis egg extracts to determine the requirements for 9-1-1 loading. We show that TopBP1 is required for the recruitment of both 9-1-1 and DNA polymerase (pol)-α to sites of replication stress. Furthermore, we show that pol-α is also directly required for Rad9 loading. Our study identifies an assembly pathway, which is controlled by TopBP1 and includes pol-α, that mediates the loading of the 9-1-1 complex onto stalled replication forks. These findings clarify early events in the assembly of checkpoint signaling complexes on DNA and identify TopBP1 as a critical sensor of replication stress. The Rockefeller University Press 2009-03-23 /pmc/articles/PMC2699152/ /pubmed/19289795 http://dx.doi.org/10.1083/jcb.200810185 Text en © 2009 Yan and Michael 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
Yan, Shan
Michael, W. Matthew
TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title_full TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title_fullStr TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title_full_unstemmed TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title_short TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
title_sort topbp1 and dna polymerase-α directly recruit the 9-1-1 complex to stalled dna replication forks
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699152/
https://www.ncbi.nlm.nih.gov/pubmed/19289795
http://dx.doi.org/10.1083/jcb.200810185
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