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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
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 | ||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| 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: |
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| 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: |
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