Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast.
Cdc48/p97
DNA-protein crosslink
UBX protein
protease
yeast
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
03 07 2023
03 07 2023
Historique:
revised:
14
04
2023
received:
25
01
2023
accepted:
24
04
2023
medline:
30
6
2023
pubmed:
5
5
2023
entrez:
5
5
2023
Statut:
ppublish
Résumé
DNA-protein crosslinks (DPCs) pose a serious threat to genome stability. The yeast proteases Wss1, 26S proteasome, and Ddi1 are safeguards of genome integrity by acting on a plethora of DNA-bound proteins in different cellular contexts. The AAA ATPase Cdc48/p97 is known to assist Wss1/SPRTN in clearing DNA-bound complexes; however, its contribution to DPC proteolysis remains unclear. Here, we show that the Cdc48 adaptor Ubx5 is detrimental in yeast mutants defective in DPC processing. Using an inducible site-specific crosslink, we show that Ubx5 accumulates at persistent DPC lesions in the absence of Wss1, which prevents their efficient removal from the DNA. Abolishing Cdc48 binding or complete loss of Ubx5 suppresses sensitivity of wss1∆ cells to DPC-inducing agents by favoring alternate repair pathways. We provide evidence for cooperation of Ubx5-Cdc48 and Wss1 in the genotoxin-induced degradation of RNA polymerase II (RNAPII), a described candidate substrate of Wss1. We propose that Ubx5-Cdc48 assists Wss1 for proteolysis of a subset of DNA-bound proteins. Together, our findings reveal a central role for Ubx5 in DPC clearance and repair.
Identifiants
pubmed: 37144685
doi: 10.15252/embj.2023113609
pmc: PMC10308373
doi:
Substances chimiques
DNA
9007-49-2
Endopeptidases
EC 3.4.-
Fungal Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e113609Subventions
Organisme : Swiss National Science Foundation
ID : 31003A_153331
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 31003A_182344
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 310030_208171
Pays : Switzerland
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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