Insert L1 is a central hub for allosteric regulation of USP1 activity.
allostery
deubiquitinating enzyme
enzyme activity
quantitative kinetic modelling
translesion synthesis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
07 04 2021
07 04 2021
Historique:
revised:
22
12
2020
received:
18
09
2020
accepted:
12
01
2021
pubmed:
24
2
2021
medline:
1
6
2021
entrez:
23
2
2021
Statut:
ppublish
Résumé
During DNA replication, the deubiquitinating enzyme USP1 limits the recruitment of translesion polymerases by removing ubiquitin marks from PCNA to allow specific regulation of the translesion synthesis (TLS) pathway. USP1 activity depends on an allosteric activator, UAF1, and this is tightly controlled. In comparison to paralogs USP12 and USP46, USP1 contains three defined inserts and lacks the second WDR20-mediated activation step. Here we show how inserts L1 and L3 together limit intrinsic USP1 activity and how this is relieved by UAF1. Intriguingly, insert L1 also conveys substrate-dependent increase in USP1 activity through DNA and PCNA interactions, in a process that is independent of UAF1-mediated activation. This study establishes insert L1 as an important regulatory hub within USP1 necessary for both substrate-mediated activity enhancement and allosteric activation upon UAF1 binding.
Identifiants
pubmed: 33619839
doi: 10.15252/embr.202051749
pmc: PMC8024992
doi:
Substances chimiques
Nuclear Proteins
0
Proliferating Cell Nuclear Antigen
0
Ubiquitin
0
Ubiquitin-Specific Proteases
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e51749Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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