RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1.
53BP1
BRCA1
DNA double-strand breaks
NHEJ
RIF1
class switch recombination
phosphorylation
poly(ADP) ribose polymerase inhibitors
shieldin
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
received:
26
04
2021
revised:
09
12
2021
accepted:
27
01
2022
pubmed:
27
2
2022
medline:
13
4
2022
entrez:
26
2
2022
Statut:
ppublish
Résumé
The chromatin-binding protein 53BP1 promotes DNA repair by orchestrating the recruitment of downstream effectors including PTIP, RIF1, and shieldin to DNA double-strand break sites. While we know how PTIP recognizes 53BP1, the molecular details of RIF1 recruitment to DNA-damage sites remains undefined. Here, we report that RIF1 is a phosphopeptide-binding protein that directly interacts with three phosphorylated 53BP1 epitopes. The RIF1-binding sites on 53BP1 share an essential LxL motif followed by two closely apposed phosphorylated residues. Simultaneous mutation of these sites on 53BP1 abrogates RIF1 accumulation into ionizing-radiation-induced foci, but surprisingly, only fully compromises 53BP1-dependent DNA repair when an alternative mode of shieldin recruitment to DNA-damage sites is also disabled. Intriguingly, this alternative mode of recruitment still depends on RIF1 but does not require its interaction with 53BP1. RIF1 therefore employs phosphopeptide recognition to promote DNA repair but also modifies shieldin action independently of 53BP1 binding.
Identifiants
pubmed: 35216668
pii: S1097-2765(22)00101-0
doi: 10.1016/j.molcel.2022.01.025
pmc: PMC8995355
mid: NIHMS1783404
pii:
doi:
Substances chimiques
BRCA1 Protein
0
Carrier Proteins
0
Phosphopeptides
0
Telomere-Binding Proteins
0
Tumor Suppressor p53-Binding Protein 1
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1359-1371.e9Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC010283
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010959
Pays : United States
Organisme : CIHR
ID : FDN143343
Pays : Canada
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests D.D. is a shareholder of and advisor to Repare Therapeutics.
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