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The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε.

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Winczura, Alicja, Appanah, Rowin, Tatham, Michael H., Hay, Ronald T. Hay and De Piccoli, Gaicomo (2019) The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε. PLoS Genetics, 15 (11). e1008427. doi:10.1371/journal.pgen.1008427

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Official URL: https://doi.org/10.1371/journal.pgen.1008427

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Abstract

Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding ability

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: PLoS Genetics
Publisher: Public Library of Science
ISSN: 1553-7390
Official Date: 25 November 2019
Dates:
DateEvent
25 November 2019Available
16 September 2019Accepted
Date of first compliant deposit: 11 November 2019
Volume: 15
Number: 11
Article Number: e1008427
DOI: 10.1371/journal.pgen.1008427
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
C44595/A16326Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
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