BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation

Dali Zong, Salomé Adam, Yifan Wang, Hiroyuki Sasanuma, Elsa Callén, Matilde Murga, Amanda Day, Michael J. Kruhlak, Nancy Wong, Meagan Munro, Arnab Ray Chaudhuri, Baktiar Karim, Bing Xia, Shunichi Takeda, Neil Johnson, Daniel Durocher, André Nussenzweig

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BRCA1 facilitates DNA end resection and RAD51 filament formation during homologous recombination. Zong et al. demonstrate that the RNF168-mediated chromatin ubiquitylation pathway acts redundantly with BRCA1 to promote RAD51-dependent homologous recombination. RNF168 activity is essential to prevent overt genome instability and tumorigenesis in BRCA1 heterozygous mice, independent of p53 mutation.

Original languageEnglish (US)
Pages (from-to)1267-1281.e7
JournalMolecular cell
Volume73
Issue number6
DOIs
StatePublished - Mar 21 2019

Fingerprint

Haploinsufficiency
Ubiquitination
Homologous Recombination
Chromatin
Genomic Instability
Carcinogenesis
Mutation
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • BRCA1
  • PALB2
  • RAD51
  • RNF168
  • cancer
  • chromatin ubiquitylation
  • genome stability
  • haploinsufficiency
  • homologous recombination
  • replication fork protection
  • resection

Cite this

Zong, D., Adam, S., Wang, Y., Sasanuma, H., Callén, E., Murga, M., ... Nussenzweig, A. (2019). BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Molecular cell, 73(6), 1267-1281.e7. https://doi.org/10.1016/j.molcel.2018.12.010
Zong, Dali ; Adam, Salomé ; Wang, Yifan ; Sasanuma, Hiroyuki ; Callén, Elsa ; Murga, Matilde ; Day, Amanda ; Kruhlak, Michael J. ; Wong, Nancy ; Munro, Meagan ; Ray Chaudhuri, Arnab ; Karim, Baktiar ; Xia, Bing ; Takeda, Shunichi ; Johnson, Neil ; Durocher, Daniel ; Nussenzweig, André. / BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. In: Molecular cell. 2019 ; Vol. 73, No. 6. pp. 1267-1281.e7.
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Zong, D, Adam, S, Wang, Y, Sasanuma, H, Callén, E, Murga, M, Day, A, Kruhlak, MJ, Wong, N, Munro, M, Ray Chaudhuri, A, Karim, B, Xia, B, Takeda, S, Johnson, N, Durocher, D & Nussenzweig, A 2019, 'BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation', Molecular cell, vol. 73, no. 6, pp. 1267-1281.e7. https://doi.org/10.1016/j.molcel.2018.12.010

BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. / Zong, Dali; Adam, Salomé; Wang, Yifan; Sasanuma, Hiroyuki; Callén, Elsa; Murga, Matilde; Day, Amanda; Kruhlak, Michael J.; Wong, Nancy; Munro, Meagan; Ray Chaudhuri, Arnab; Karim, Baktiar; Xia, Bing; Takeda, Shunichi; Johnson, Neil; Durocher, Daniel; Nussenzweig, André.

In: Molecular cell, Vol. 73, No. 6, 21.03.2019, p. 1267-1281.e7.

Research output: Contribution to journalArticle

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AU - Zong, Dali

AU - Adam, Salomé

AU - Wang, Yifan

AU - Sasanuma, Hiroyuki

AU - Callén, Elsa

AU - Murga, Matilde

AU - Day, Amanda

AU - Kruhlak, Michael J.

AU - Wong, Nancy

AU - Munro, Meagan

AU - Ray Chaudhuri, Arnab

AU - Karim, Baktiar

AU - Xia, Bing

AU - Takeda, Shunichi

AU - Johnson, Neil

AU - Durocher, Daniel

AU - Nussenzweig, André

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AB - BRCA1 facilitates DNA end resection and RAD51 filament formation during homologous recombination. Zong et al. demonstrate that the RNF168-mediated chromatin ubiquitylation pathway acts redundantly with BRCA1 to promote RAD51-dependent homologous recombination. RNF168 activity is essential to prevent overt genome instability and tumorigenesis in BRCA1 heterozygous mice, independent of p53 mutation.

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Zong D, Adam S, Wang Y, Sasanuma H, Callén E, Murga M et al. BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Molecular cell. 2019 Mar 21;73(6):1267-1281.e7. https://doi.org/10.1016/j.molcel.2018.12.010