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Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability
DNA replication and RNA transcription compete for the same substrate during S phase. Cells have evolved several mechanisms to minimize such conflicts. Here, we identify the mechanism by which the transcription termination helicase Sen1 associates with replisomes. We show that the N terminus of Sen1...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034062/ https://www.ncbi.nlm.nih.gov/pubmed/32075754 http://dx.doi.org/10.1016/j.celrep.2020.01.087 |
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author | Appanah, Rowin Lones, Emma Claire Aiello, Umberto Libri, Domenico De Piccoli, Giacomo |
author_facet | Appanah, Rowin Lones, Emma Claire Aiello, Umberto Libri, Domenico De Piccoli, Giacomo |
author_sort | Appanah, Rowin |
collection | PubMed |
description | DNA replication and RNA transcription compete for the same substrate during S phase. Cells have evolved several mechanisms to minimize such conflicts. Here, we identify the mechanism by which the transcription termination helicase Sen1 associates with replisomes. We show that the N terminus of Sen1 is both sufficient and necessary for replisome association and that it binds to the replisome via the components Ctf4 and Mrc1. We generated a separation of function mutant, sen1-3, which abolishes replisome binding without affecting transcription termination. We observe that the sen1-3 mutants show increased genome instability and recombination levels. Moreover, sen1-3 is synthetically defective with mutations in genes involved in RNA metabolism and the S phase checkpoint. RNH1 overexpression suppresses defects in the former, but not the latter. These findings illustrate how Sen1 plays a key function at replication forks during DNA replication to promote fork progression and chromosome stability. |
format | Online Article Text |
id | pubmed-7034062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70340622020-02-27 Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability Appanah, Rowin Lones, Emma Claire Aiello, Umberto Libri, Domenico De Piccoli, Giacomo Cell Rep Article DNA replication and RNA transcription compete for the same substrate during S phase. Cells have evolved several mechanisms to minimize such conflicts. Here, we identify the mechanism by which the transcription termination helicase Sen1 associates with replisomes. We show that the N terminus of Sen1 is both sufficient and necessary for replisome association and that it binds to the replisome via the components Ctf4 and Mrc1. We generated a separation of function mutant, sen1-3, which abolishes replisome binding without affecting transcription termination. We observe that the sen1-3 mutants show increased genome instability and recombination levels. Moreover, sen1-3 is synthetically defective with mutations in genes involved in RNA metabolism and the S phase checkpoint. RNH1 overexpression suppresses defects in the former, but not the latter. These findings illustrate how Sen1 plays a key function at replication forks during DNA replication to promote fork progression and chromosome stability. Cell Press 2020-02-18 /pmc/articles/PMC7034062/ /pubmed/32075754 http://dx.doi.org/10.1016/j.celrep.2020.01.087 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Appanah, Rowin Lones, Emma Claire Aiello, Umberto Libri, Domenico De Piccoli, Giacomo Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title | Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title_full | Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title_fullStr | Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title_full_unstemmed | Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title_short | Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability |
title_sort | sen1 is recruited to replication forks via ctf4 and mrc1 and promotes genome stability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034062/ https://www.ncbi.nlm.nih.gov/pubmed/32075754 http://dx.doi.org/10.1016/j.celrep.2020.01.087 |
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