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Bakr A, Hey J, Sigismondo G, et al. ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition. Nucleic Acids Res. 2021;49(20):11666-11689doi: 10.1093/nar/gkab964.
Bakr, A., Hey, J., Sigismondo, G., Liu, C. S., Sadik, A., Goyal, A., Cross, A., Iyer, R. L., Müller, P., Trauernicht, M., Breuer, K., Lutsik, P., Opitz, C. A., Krijgsveld, J., Weichenhan, D., Plass, C., Popanda, O., & Schmezer, P. (2021). ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition. Nucleic acids research, 49(20), 11666-11689. https://doi.org/10.1093/nar/gkab964
Bakr, Ali, et al. "ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition." Nucleic acids research vol. 49,20 (2021): 11666-11689. doi: https://doi.org/10.1093/nar/gkab964
Bakr A, Hey J, Sigismondo G, Liu CS, Sadik A, Goyal A, Cross A, Iyer RL, Müller P, Trauernicht M, Breuer K, Lutsik P, Opitz CA, Krijgsveld J, Weichenhan D, Plass C, Popanda O, Schmezer P. ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition. Nucleic Acids Res. 2021 Nov 18;49(20):11666-11689. doi: 10.1093/nar/gkab964. PMID: 34718742; PMCID: PMC8599806.
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Nucleic Acids Res. 2021 Nov 18;49(20):11666-11689. doi: 10.1093/nar/gkab964.

ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.

Nucleic acids research

Ali Bakr, Joschka Hey, Gianluca Sigismondo, Chun-Shan Liu, Ahmed Sadik, Ashish Goyal, Alice Cross, Ramya Lakshmana Iyer, Patrick Müller, Max Trauernicht, Kersten Breuer, Pavlo Lutsik, Christiane A Opitz, Jeroen Krijgsveld, Dieter Weichenhan, Christoph Plass, Odilia Popanda, Peter Schmezer

Affiliations

  1. Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), INF280, 69120 Heidelberg, Germany.
  2. Heidelberg University, Faculty of Biosciences, 69120 Heidelberg, Germany.
  3. Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), INF581, 69120 Heidelberg, Germany.
  4. DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  5. Imperial College London, London, SW7 2AZ, UK.
  6. Neurology Clinic and National Center for Tumor Diseases, Heidelberg University Hospital, 69120 Heidelberg, Germany.
  7. Heidelberg University, Medical Faculty, INF672, 69120, Heidelberg, Germany.
  8. German Cancer Consortium (DKTK), INF280, 69120 Heidelberg, Germany.

PMID: 34718742 PMCID: PMC8599806 DOI: 10.1093/nar/gkab964

Abstract

The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors.

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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