Replication forks terminate at TERs and telomeres. Forks that converge or encounter transcription generate topological stress. Combining genetics, genomics, and transmission electron microscopy, we find that Rrm3hPif1 and Sen1hSenataxin helicases assist termination at TERs; Sen1 specifically acts at telomeres. rrm3 and sen1 genetically interact and fail to terminate replication, exhibiting fragility at termination zones (TERs) and telomeres. sen1rrm3 accumulates RNA-DNA hybrids and X-shaped gapped or reversed converging forks at TERs; sen1, but not rrm3, builds up RNA polymerase II (RNPII) at TERs and telomeres. Rrm3 and Sen1 restrain Top1 and Top2 activities, preventing toxic accumulation of positive supercoil at TERs and telomeres. We suggest that Rrm3 and Sen1 coordinate the activities of Top1 and Top2 when forks encounter transcription head on or codirectionally, respectively, thus preventing the slowing down of DNA and RNA polymerases. Hence Rrm3 and Sen1 are indispensable to generate permissive topological conditions for replication termination.

Sen1 and Rrm3 ensure permissive topological conditions for replication termination / R. Choudhary, J. Niska-Blakie, M. Adhil, G. Liberi, Y. Achar, M. Giannattasio, M. Foiani. - In: CELL REPORTS. - ISSN 2211-1247. - 42:7(2023 Jul 25), pp. 112747.1-112747.23. [10.1016/j.celrep.2023.112747]

Sen1 and Rrm3 ensure permissive topological conditions for replication termination

R. Choudhary
Primo
;
G. Liberi;M. Giannattasio
Penultimo
;
M. Foiani
Ultimo
2023

Abstract

Replication forks terminate at TERs and telomeres. Forks that converge or encounter transcription generate topological stress. Combining genetics, genomics, and transmission electron microscopy, we find that Rrm3hPif1 and Sen1hSenataxin helicases assist termination at TERs; Sen1 specifically acts at telomeres. rrm3 and sen1 genetically interact and fail to terminate replication, exhibiting fragility at termination zones (TERs) and telomeres. sen1rrm3 accumulates RNA-DNA hybrids and X-shaped gapped or reversed converging forks at TERs; sen1, but not rrm3, builds up RNA polymerase II (RNPII) at TERs and telomeres. Rrm3 and Sen1 restrain Top1 and Top2 activities, preventing toxic accumulation of positive supercoil at TERs and telomeres. We suggest that Rrm3 and Sen1 coordinate the activities of Top1 and Top2 when forks encounter transcription head on or codirectionally, respectively, thus preventing the slowing down of DNA and RNA polymerases. Hence Rrm3 and Sen1 are indispensable to generate permissive topological conditions for replication termination.
CP: Molecular biology; DNA topology; RNPII; Rrm3; Senataxin; Top1; Top2; replication termination; telomeres;
Settore BIO/11 - Biologia Molecolare
Settore BIO/18 - Genetica
Settore BIO/13 - Biologia Applicata
25-lug-2023
Article (author)
File in questo prodotto:
File Dimensione Formato  
ChoudharyetalCellreports2023.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 23.11 MB
Formato Adobe PDF
23.11 MB Adobe PDF Visualizza/Apri
ChoudharyetalCellreports2023_compressed.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 8.92 MB
Formato Adobe PDF
8.92 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/985268
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact