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Updated: Oct 25, 2025

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions
06:55

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions

Published on: June 7, 2020

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Interaction with the CCT chaperonin complex limits APOBEC3A cytidine deaminase cytotoxicity

Abby M Green1,2, Rachel A DeWeerd1, David R O'Leary1

  • 1Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.

EMBO Reports
|August 4, 2021
PubMed

Insights

The chaperonin-containing TCP-1 (CCT) complex regulates APOBEC3A (A3A) enzyme activity. Disruption of CCT function increases A3A-induced DNA damage and mutations, impacting cancer genomes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • APOBEC3 cytidine deaminases cause somatic mutations in cancer genomes.
  • APOBEC3 enzymes normally restrict viral genomes but can mutate cellular DNA.
  • Regulation of APOBEC3 activity and cellular DNA interaction is poorly understood.

Purpose of the Study:

  • To identify regulators of APOBEC3A (A3A) activity using proteomics.
  • To investigate the role of protein interactors in A3A-mediated mutagenesis.
  • To explore the link between CCT complex function and A3A mutational signatures in cancer.

Main Methods:

  • Proteomic analysis to identify A3A protein interactors.
  • Depletion studies to assess the impact of CCT complex on A3A activity.
  • Bioinformatic evaluation of cancer genomes for mutational signatures.

Main Results:

  • The chaperonin-containing TCP-1 (CCT) complex was identified as an A3A interactor.
  • Depletion of CCT led to increased A3A-induced DNA damage and cytotoxicity.
  • Cancer genomes showed enrichment of A3A mutational signatures in tumors with CCT gene mutations.

Conclusions:

  • The CCT complex interacts with and likely regulates A3A activity.
  • Disruption of CCT function enhances A3A-mediated mutagenesis.
  • CCT complex dysfunction contributes to A3A mutational patterns in cancer.
Keywords:
APOBEC3ACCT chaperonincytidine deaminasemutational signaturesprotein interaction

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