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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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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. |
format | Online Article Text |
id | pubmed-4539992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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