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Sen1 is recruited to replication forks via Ctf4 and Mrc1 and promotes genome stability

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Appanah, Rowin, Lones, E. C., Aiello, U., Libri, D. and De Piccoli, Giacomo (2020) Sen1 is recruited to replication forks via Ctf4 and Mrc1 and promotes genome stability. Cell Reports, 30 (7). P2094-2105.E9. doi:10.1016/j.celrep.2020.01.087

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Official URL: https://doi.org/10.1016/j.celrep.2020.01.087

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): DNA replication, RNA, Genetic transcription, Genomes
Journal or Publication Title: Cell Reports
Publisher: Elsevier
ISSN: 2211-1247
Official Date: 18 February 2020
Dates:
DateEvent
18 February 2020Available
20 December 2019Accepted
Date of first compliant deposit: 23 January 2020
Volume: 30
Number: 7
Page Range: P2094-2105.E9
DOI: 10.1016/j.celrep.2020.01.087
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
C44595/A16326 Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
Chancellor International ScholarshipUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
MIBTP program[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIED[CNRS] Centre National de la Recherche Scientifiquehttp://dx.doi.org/10.13039/501100004794
ANR-12-BSV8-0014-01 [ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
ANR-16-CE12-0022-01[ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
ANR-11-LABX-0071[ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
Idex ANR-11-IDEX-0005-02[ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
UNSPECIFIEDMinistère de l'Enseignement Supérieur et de la RechercheUNSPECIFIED
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