Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Appanah, Rowin, Lones, Emma Claire, Aiello, Umberto, Libri, Domenico, De Piccoli, Giacomo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
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
_version_ 1783499803143962624
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
work_keys_str_mv AT appanahrowin sen1isrecruitedtoreplicationforksviactf4andmrc1andpromotesgenomestability
AT lonesemmaclaire sen1isrecruitedtoreplicationforksviactf4andmrc1andpromotesgenomestability
AT aielloumberto sen1isrecruitedtoreplicationforksviactf4andmrc1andpromotesgenomestability
AT libridomenico sen1isrecruitedtoreplicationforksviactf4andmrc1andpromotesgenomestability
AT depiccoligiacomo sen1isrecruitedtoreplicationforksviactf4andmrc1andpromotesgenomestability