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The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress
Human cells lacking RIF1 are highly sensitive to replication inhibitors, but the reasons for this sensitivity have been enigmatic. Here, we show that RIF1 must be present both during replication stress and in the ensuing recovery period to promote cell survival. Of two isoforms produced by alternati...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671687/ https://www.ncbi.nlm.nih.gov/pubmed/33141022 http://dx.doi.org/10.7554/eLife.58020 |
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author | Watts, Lotte P Natsume, Toyoaki Saito, Yuichiro Garzon, Javier Dong, Qianqian Boteva, Lora Gilbert, Nick Kanemaki, Masato T Hiraga, Shin-ichiro Donaldson, Anne D |
author_facet | Watts, Lotte P Natsume, Toyoaki Saito, Yuichiro Garzon, Javier Dong, Qianqian Boteva, Lora Gilbert, Nick Kanemaki, Masato T Hiraga, Shin-ichiro Donaldson, Anne D |
author_sort | Watts, Lotte P |
collection | PubMed |
description | Human cells lacking RIF1 are highly sensitive to replication inhibitors, but the reasons for this sensitivity have been enigmatic. Here, we show that RIF1 must be present both during replication stress and in the ensuing recovery period to promote cell survival. Of two isoforms produced by alternative splicing, we find that RIF1-Long alone can protect cells against replication inhibition, but RIF1-Short is incapable of mediating protection. Consistent with this isoform-specific role, RIF1-Long is required to promote the formation of the 53BP1 nuclear bodies that protect unrepaired damage sites in the G1 phase following replication stress. Overall, our observations show that RIF1 is needed at several cell cycle stages after replication insult, with the RIF1-Long isoform playing a specific role during the ensuing G1 phase in damage site protection. |
format | Online Article Text |
id | pubmed-7671687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-76716872020-11-18 The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress Watts, Lotte P Natsume, Toyoaki Saito, Yuichiro Garzon, Javier Dong, Qianqian Boteva, Lora Gilbert, Nick Kanemaki, Masato T Hiraga, Shin-ichiro Donaldson, Anne D eLife Cell Biology Human cells lacking RIF1 are highly sensitive to replication inhibitors, but the reasons for this sensitivity have been enigmatic. Here, we show that RIF1 must be present both during replication stress and in the ensuing recovery period to promote cell survival. Of two isoforms produced by alternative splicing, we find that RIF1-Long alone can protect cells against replication inhibition, but RIF1-Short is incapable of mediating protection. Consistent with this isoform-specific role, RIF1-Long is required to promote the formation of the 53BP1 nuclear bodies that protect unrepaired damage sites in the G1 phase following replication stress. Overall, our observations show that RIF1 is needed at several cell cycle stages after replication insult, with the RIF1-Long isoform playing a specific role during the ensuing G1 phase in damage site protection. eLife Sciences Publications, Ltd 2020-11-03 /pmc/articles/PMC7671687/ /pubmed/33141022 http://dx.doi.org/10.7554/eLife.58020 Text en © 2020, Watts et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Watts, Lotte P Natsume, Toyoaki Saito, Yuichiro Garzon, Javier Dong, Qianqian Boteva, Lora Gilbert, Nick Kanemaki, Masato T Hiraga, Shin-ichiro Donaldson, Anne D The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title | The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title_full | The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title_fullStr | The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title_full_unstemmed | The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title_short | The RIF1-long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress |
title_sort | rif1-long splice variant promotes g1 phase 53bp1 nuclear bodies to protect against replication stress |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671687/ https://www.ncbi.nlm.nih.gov/pubmed/33141022 http://dx.doi.org/10.7554/eLife.58020 |
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