53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark
Open accessAbstract
53BP1 (also called TP53BP1) is a chromatin-associated factor that promotes immunoglobulin class switching and DNA double-strand-break (DSB) repair by non-homologous end joining. To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase. How ubiquitin recruits 53BP1 to break sites remains unknown as its relocalization involves recognition of histone H4 Lys 20 (H4K20) methylation by its Tudor domain. Here we elucidate how vertebrate 53BP1 is recruited to the chromatin that flanks DSB sites. We show that 53BP1 recognizes mononucleosomes containing dimethylated H4K20 (H4K20me2) and H2A ubiquitinated on Lys 15 (H2AK15ub), the latter being a product of RNF168 action on chromatin. 53BP1 binds to nucleosomes minimally as a dimer using its previously characterized methyl-lysine-binding Tudor domain and a carboxy-terminal extension, termed the ubiquitination-dependent recruitment (UDR) motif, which interacts with the epitope formed by H2AK15ub and its surrounding residues on the H2A tail. 53BP1 is therefore a bivalent histone modification reader that recognizes a histone 'code' produced by DSB signalling.
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- Authors
- Fradet-Turcotte, A., Canny, M. D., Escribano-Díaz, C., Orthwein, A., Leung, C. C. Y., Huang, H., Landry, M.-C., Kitevski-LeBlanc, J., Noordermeer, S. M., Sicheri, F., & Durocher, D.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Corresponding author
- Durocher, Daniel
- ORCID
- Venue
- Nature
- Published
- 2013-06-12
- Volume
- 499
- Issue
- 7456
- Pages
- 50-54
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3955401
- OpenAlex
- W1988259427
- Cited by
- 686
- References
- 40
- Citations by year
- 2026: 21 · 2025: 35 · 2024: 51 · 2023: 37 · 2022: 49 · 2021: 62 · 2020: 55 · 2019: 65 · 2018: 58 · 2017: 76 · 2016: 53 · 2015: 56 · 2014: 44 · 2013: 23
- FWCI
- 26.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Canadian Institutes of Health Research (84297_2, MOP84297, 84297_1)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- 53BP1, RNF168, DNA double-strand break repair, non-homologous end joining, Tudor domain, DNA damage response
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Amino Acid Sequence, Animals, Cell Line, Chromosomal Proteins, Non-Histone, DNA Damage, DNA-Binding Proteins, Female, Histones, Humans, Lysine, Male, Molecular Sequence Data, Nuclear Proteins, Nucleosomes, Protein Binding, Schizosaccharomyces, Signal Transduction, Protein Structure, Tertiary, Cell Cycle Proteins, Amino Acid Motifs, Ubiquitin, Schizosaccharomyces pombe Proteins, Intracellular Signaling Peptides and Proteins, Mutant Proteins, Mice, DNA Breaks, Double-Stranded, Ubiquitination
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