Cited by 522DNA Repair MechanismsPARP inhibition in cancer therapyGenomics and Chromatin Dynamics

Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination

Open access
Tang, Jiangbo, Cho, Nam Woo, Cui, Gaofeng, Manion, Erica M, Shanbhag, Niraj M, Botuyan, Maria Victoria, Mer, Georges, Greenberg, Roger A·2013·Nature Structural & Molecular Biology

Abstract

The pathogenic sequelae of BRCA1 mutation in human and mouse cells are mitigated by concomitant deletion of 53BP1, which binds histone H4 dimethylated at Lys20 (H4K20me2) to promote nonhomologous end joining, suggesting that a balance between BRCA1 and 53BP1 regulates DNA double strand-break (DSB) repair mechanism choice. Here we document that acetylation is a key determinant of this balance. TIP60 acetyltransferase deficiency reduced BRCA1 at DSB chromatin with commensurate increases in 53BP1, whereas HDAC inhibition yielded the opposite effect. TIP60-dependent H4 acetylation diminished 53BP1 binding to H4K20me2 in part through disruption of a salt bridge between H4K16 and Glu1551 in the 53BP1 Tudor domain. Moreover, TIP60 deficiency impaired homologous recombination and conferred sensitivity to PARP inhibition in a 53BP1-dependent manner. These findings demonstrate that acetylation in cis to H4K20me2 regulates relative BRCA1 and 53BP1 DSB chromatin occupancy to direct DNA repair mechanism.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nsmb.2499

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 58 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Tang, J., Cho, N. W., Cui, G., Manion, E. M., Shanbhag, N. M., Botuyan, M. V., Mer, G., & Greenberg, R. A.
Affiliations
  • University of Pennsylvania (US)
  • Mayo Clinic (US)
Corresponding author
Greenberg, Roger A
Venue
Nature Structural & Molecular Biology
Published
2013-02-03
Volume
20
Issue
3
Pages
317-325
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2060247906
Cited by
521
References
58
Citations by year
2026: 20 · 2025: 26 · 2024: 28 · 2023: 29 · 2022: 52 · 2021: 45 · 2020: 48 · 2019: 34 · 2018: 48 · 2017: 49 · 2016: 53 · 2015: 35 · 2014: 33 · 2013: 21
FWCI
21.37
Type
journal article
Language
en
Open access
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA138835, R01CA132878, R01CA174904, P50CA116201, P30CA016520)
  • National Institute of General Medical Sciences (R01GM101149)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
53BP1, BRCA1, histone H4 acetylation, H4K16 acetylation, Tip60, H4K20me2, homologous recombination, non-homologous end joining, DNA double-strand break repair, DNA repair pathway choice, Tudor domain, histone deacetylase inhibition, chromatin binding
MeSH terms
Tumor Suppressor p53-Binding Protein 1, ATPases Associated with Diverse Cellular Activities, Lysine Acetyltransferase 5, Acetylation, Amino Acid Sequence, Carrier Proteins, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Histone Deacetylases, Histones, Humans, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Protein Conformation, BRCA1 Protein, Intracellular Signaling Peptides and Proteins, Histone Acetyltransferases, DNA Breaks, Double-Stranded, Gene Knockdown Techniques, Homologous Recombination

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review