Skip to main content

Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination.

Publication ,  Journal Article
Moquin, DM; Genois, M-M; Zhang, J-M; Ouyang, J; Yadav, T; Buisson, R; Yazinski, SA; Tan, J; Boukhali, M; Gagné, J-P; Poirier, GG; Lan, L ...
Published in: Genes Dev
January 1, 2019

Numerous DNA repair and signaling proteins function at DNA damage sites to protect the genome. Here, we show that fusion of the promiscuous biotin ligase BirAR118G with RAD18 leads to localized protein biotinylation at DNA damage sites, allowing identification of ZPET (zinc finger protein proximal to RAD eighteen)/ZNF280C as a potential DNA damage response (DDR) protein. ZPET binds ssDNA and localizes to DNA double-strand breaks (DSBs) and stalled replication forks. In vitro, ZPET inhibits MRE11 binding to ssDNA. In cells, ZPET delays MRE11 binding to chromatin after DSB formation and slows DNA end resection through binding ssDNA. ZPET hinders resection independently of 53BP1 and HELB. Cells lacking ZPET displayed enhanced homologous recombination (HR), accelerated replication forks under stress, and increased resistance to DSBs and PARP inhibition. These results not only reveal ZPET as an HR repressor but also suggest that localized protein biotinylation at DNA damage sites is a useful strategy to identify DDR proteins.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Genes Dev

DOI

EISSN

1549-5477

Publication Date

January 1, 2019

Volume

33

Issue

1-2

Start / End Page

75 / 89

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transcription Factors
  • Repressor Proteins
  • Protein Transport
  • Protein Binding
  • MRE11 Homologue Protein
  • Humans
  • Homologous Recombination
  • Gene Knockdown Techniques
  • Escherichia coli Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moquin, D. M., Genois, M.-M., Zhang, J.-M., Ouyang, J., Yadav, T., Buisson, R., … Zou, L. (2019). Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination. Genes Dev, 33(1–2), 75–89. https://doi.org/10.1101/gad.315978.118
Moquin, David M., Marie-Michelle Genois, Jia-Min Zhang, Jian Ouyang, Tribhuwan Yadav, Rémi Buisson, Stephanie A. Yazinski, et al. “Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination.Genes Dev 33, no. 1–2 (January 1, 2019): 75–89. https://doi.org/10.1101/gad.315978.118.
Moquin DM, Genois M-M, Zhang J-M, Ouyang J, Yadav T, Buisson R, et al. Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination. Genes Dev. 2019 Jan 1;33(1–2):75–89.
Moquin, David M., et al. “Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination.Genes Dev, vol. 33, no. 1–2, Jan. 2019, pp. 75–89. Pubmed, doi:10.1101/gad.315978.118.
Moquin DM, Genois M-M, Zhang J-M, Ouyang J, Yadav T, Buisson R, Yazinski SA, Tan J, Boukhali M, Gagné J-P, Poirier GG, Lan L, Haas W, Zou L. Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination. Genes Dev. 2019 Jan 1;33(1–2):75–89.

Published In

Genes Dev

DOI

EISSN

1549-5477

Publication Date

January 1, 2019

Volume

33

Issue

1-2

Start / End Page

75 / 89

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transcription Factors
  • Repressor Proteins
  • Protein Transport
  • Protein Binding
  • MRE11 Homologue Protein
  • Humans
  • Homologous Recombination
  • Gene Knockdown Techniques
  • Escherichia coli Proteins