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Updated: Oct 6, 2025

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Visualization of DNA Repair Proteins Interaction by Immunofluorescence

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CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival

Jordi Minguillón1,2, María José Ramírez1,2, Llorenç Rovirosa1,2

  • 1Genomic Instability Syndromes and DNA Repair Group and Join Research Unit on Genomic Medicine UAB-Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.

Cancers
|January 21, 2022
PubMed

Insights

The tumor suppressor CDK5RAP3 negatively regulates DNA repair, and its low expression correlates with poor breast cancer survival. Genetic variations in CDK5RAP3 may also impact cancer risk in BRCA mutation carriers.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • BRCA2 is crucial for DNA repair, and its mutations increase breast and ovarian cancer risk.
  • Mutations in BRCA2-interacting proteins can affect cancer risk and sensitivity to DNA damage.

Purpose of the Study:

  • To identify novel BRCA2-interacting proteins.
  • To investigate the role of CDK5RAP3 in DNA repair and cancer.
  • To explore the association of CDK5RAP3 with breast and ovarian cancer risk.

Main Methods:

  • Protein-protein interaction studies to identify CDK5RAP3 as a BRCA2 interactor.
  • Cellular assays to assess DNA repair mechanisms (homologous recombination, single-strand annealing) and genomic instability upon CDK5RAP3 depletion.
  • Transcriptomic data analysis to correlate CDK5RAP3 expression with patient survival.
  • Genetic association studies in BRCA1 and BRCA2 mutation carriers.

Main Results:

  • CDK5RAP3 was identified as a novel BRCA2-interacting protein.
  • CDK5RAP3 depletion enhanced DNA damage resistance and homologous recombination.
  • Low CDK5RAP3 tumor expression was linked to poorer breast cancer survival.
  • Genetic variations in CDK5RAP3 may influence cancer risk in BRCA mutation carriers.

Conclusions:

  • CDK5RAP3 negatively regulates double-strand break repair in S-phase.
  • CDK5RAP3 is a critical factor in DNA repair and influences breast cancer outcomes.
  • CDK5RAP3 warrants further investigation as a potential therapeutic target and biomarker.
Keywords:
BRCA2CDK5RAP3DNA repairbreast cancerchemoresistance

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