CARM1 regulates replication fork speed and stress response by stimulating PARP1.
CARM1
PARP1
PARylation
PrimPol
RECQ1
fork reversal
fork speed
replication fork
replication stress
translesion synthesis
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
18 02 2021
18 02 2021
Historique:
received:
12
05
2020
revised:
19
10
2020
accepted:
02
12
2020
pubmed:
8
1
2021
medline:
3
3
2021
entrez:
7
1
2021
Statut:
ppublish
Résumé
DNA replication forks use multiple mechanisms to deal with replication stress, but how the choice of mechanisms is made is still poorly understood. Here, we show that CARM1 associates with replication forks and reduces fork speed independently of its methyltransferase activity. The speeding of replication forks in CARM1-deficient cells requires RECQ1, which resolves reversed forks, and RAD18, which promotes translesion synthesis. Loss of CARM1 reduces fork reversal and increases single-stranded DNA (ssDNA) gaps but allows cells to tolerate higher replication stress. Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. In vitro, CARM1 stimulates PARP1 activity by enhancing its DNA binding and acts jointly with HPF1 to activate PARP1. Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms.
Identifiants
pubmed: 33412112
pii: S1097-2765(20)30902-3
doi: 10.1016/j.molcel.2020.12.010
pmc: PMC7897296
mid: NIHMS1657266
pii:
doi:
Substances chimiques
Carrier Proteins
0
HPF1 protein, human
0
Nuclear Proteins
0
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
coactivator-associated arginine methyltransferase 1
EC 2.1.1.319
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
RECQL protein, human
EC 3.6.1.-
RecQ Helicases
EC 3.6.4.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
784-800.e8Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM126421
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248526
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218856
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197779
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237263
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests L.Z. is a member of the advisory board of Molecular Cell. The authors declare no competing interests.
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