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TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic...

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Autores principales: Pedersen, Rune Troelsgaard, Kruse, Thomas, Nilsson, Jakob, Oestergaard, Vibe H., Lisby, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539992/
https://www.ncbi.nlm.nih.gov/pubmed/26283799
http://dx.doi.org/10.1083/jcb.201502107
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author Pedersen, Rune Troelsgaard
Kruse, Thomas
Nilsson, Jakob
Oestergaard, Vibe H.
Lisby, Michael
author_facet Pedersen, Rune Troelsgaard
Kruse, Thomas
Nilsson, Jakob
Oestergaard, Vibe H.
Lisby, Michael
author_sort Pedersen, Rune Troelsgaard
collection PubMed
description Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis.
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spelling pubmed-45399922016-02-17 TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells Pedersen, Rune Troelsgaard Kruse, Thomas Nilsson, Jakob Oestergaard, Vibe H. Lisby, Michael J Cell Biol Research Articles Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. The Rockefeller University Press 2015-08-17 /pmc/articles/PMC4539992/ /pubmed/26283799 http://dx.doi.org/10.1083/jcb.201502107 Text en © 2015 Pedersen et al. 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.rupress.org/terms). 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
Pedersen, Rune Troelsgaard
Kruse, Thomas
Nilsson, Jakob
Oestergaard, Vibe H.
Lisby, Michael
TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title_full TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title_fullStr TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title_full_unstemmed TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title_short TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells
title_sort topbp1 is required at mitosis to reduce transmission of dna damage to g1 daughter cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539992/
https://www.ncbi.nlm.nih.gov/pubmed/26283799
http://dx.doi.org/10.1083/jcb.201502107
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