Replication stress activates the Mec1ATR and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes. Here, we show that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites, are detrimental in rad53 mutants experiencing replication stress. Rrm3 and Pif1 ablations rescue cell lethality, chromosome fragmentation, replisome-fork dissociation, fork reversal, and processing in rad53 cells. Through phosphorylation, Rad53 regulates Rrm3 and Pif1; phospho-mimicking rrm3 mutants ameliorate rad53 phenotypes following replication stress without affecting replication across pausing elements under normal conditions. Hence, the Mec1-Rad53 axis protects fork stability by regulating nuclear pores and DNA helicases. We propose that following replication stress, forks stall in an asymmetric conformation by inhibiting Rrm3 and Pif1, thus impeding lagging strand extension and preventing fork reversal; conversely, under unperturbed conditions, the peculiar conformation of forks encountering pausing sites would depend on active Rrm3 and Pif1.

Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress / S.E. Rossi, A. Ajazi, W. Carotenuto, M. Foiani, M. Giannattasio. - In: CELL REPORTS. - ISSN 2211-1247. - 13:1(2015 Oct), pp. 80-92. [10.1016/j.celrep.2015.08.073]

Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress

S.E. Rossi
Primo
;
A. Ajazi
Secondo
;
W. Carotenuto;M. Foiani
Penultimo
;
M. Giannattasio
Ultimo
2015

Abstract

Replication stress activates the Mec1ATR and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes. Here, we show that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites, are detrimental in rad53 mutants experiencing replication stress. Rrm3 and Pif1 ablations rescue cell lethality, chromosome fragmentation, replisome-fork dissociation, fork reversal, and processing in rad53 cells. Through phosphorylation, Rad53 regulates Rrm3 and Pif1; phospho-mimicking rrm3 mutants ameliorate rad53 phenotypes following replication stress without affecting replication across pausing elements under normal conditions. Hence, the Mec1-Rad53 axis protects fork stability by regulating nuclear pores and DNA helicases. We propose that following replication stress, forks stall in an asymmetric conformation by inhibiting Rrm3 and Pif1, thus impeding lagging strand extension and preventing fork reversal; conversely, under unperturbed conditions, the peculiar conformation of forks encountering pausing sites would depend on active Rrm3 and Pif1.
No
English
Biochemistry, Genetics and Molecular Biology (all)
Settore BIO/11 - Biologia Molecolare
Articolo
Nessuno
Pubblicazione scientifica
ott-2015
Elsevier
13
1
80
92
13
Pubblicato
Periodico con rilevanza internazionale
scopus
pubmed
crossref
Aderisco
info:eu-repo/semantics/article
Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress / S.E. Rossi, A. Ajazi, W. Carotenuto, M. Foiani, M. Giannattasio. - In: CELL REPORTS. - ISSN 2211-1247. - 13:1(2015 Oct), pp. 80-92. [10.1016/j.celrep.2015.08.073]
open
Prodotti della ricerca::01 - Articolo su periodico
5
262
Article (author)
no
S.E. Rossi, A. Ajazi, W. Carotenuto, M. Foiani, M. Giannattasio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/342064
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