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Cited by 43DNA Repair MechanismsGenomics and Chromatin DynamicsEffects of Radiation Exposure

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RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1

Open access
Setiaputra, Dheva, Escribano-Díaz, Cristina, Reinert, Julia K., Sadana, Pooja, Zong, Dali, Callen, Elsa, Sifri, Chérine, Seebacher, Jan, Nussenzweig, André, Thomä, Nicolas H., Durocher, Daniel·2022·Molecular Cell
DOI 10.1016/j.molcel.2022.01.025PMC PMC8995355

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Abstract

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.

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Metadata

Authors
Setiaputra, D., Escribano-Díaz, C., Reinert, J. K., Sadana, P., Zong, D., Callen, E., Sifri, C., Seebacher, J., Nussenzweig, A., Thomä, N. H., & Durocher, D.
Affiliations
  • Mount Sinai Hospital (CA)
  • University of Basel (CH)
  • Friedrich Miescher Institute (CH)
  • National Institutes of Health (US)
Corresponding author
  • Setiaputra, Dheva
  • Durocher, Daniel
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2022-04
Volume
82
Issue
7
Pages
1359-1371.e9
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2022.01.025
PMC
PMC8995355
OpenAlex
W4225875678
Cited by
43
References
5
Citations by year
2026: 5 · 2025: 18 · 2024: 5 · 2023: 7 · 2022: 6
FWCI
2.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Boehringer Ingelheim Fonds
  • National Institutes of Health
  • Canadian Institutes of Health Research (FDN143343 ()
  • National Cancer Institute (ZIABC010283, ZIABC010959)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
RIF1, 53BP1, phosphopeptide recognition, DNA double-strand break repair, PTIP, ionizing radiation-induced foci, chromatin-binding proteins, DNA damage response
MeSH terms
Tumor Suppressor p53-Binding Protein 1, Carrier Proteins, DNA, DNA Repair, Phosphopeptides, BRCA1 Protein, Telomere-Binding Proteins, DNA End-Joining Repair

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