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OB-Folds and Genome Maintenance: Targeting Protein-DNA Interactions for Cancer Therapy

Sui Par1, Sofia Vaides1, Pamela S VanderVere-Carozza2

  • 1Indiana University Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Cancers
|July 20, 2021
PubMed

Insights

Oligonucleotide/oligosaccharide binding folds (OB-folds) are crucial for DNA binding proteins involved in genome stability and cancer. Targeting these OB-fold proteins shows promise for novel cancer therapeutics.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Oncology

Background:

  • Genome stability pathways are essential for preventing mutations and diseases like cancer.
  • Many DNA-binding proteins utilize oligonucleotide/oligosaccharide binding folds (OB-folds) for DNA interaction.
  • OB-folds mediate sequence-independent binding to single-stranded DNA (ssDNA), positioning proteins for DNA metabolism.

Purpose of the Study:

  • To review the structural organization of OB-fold proteins relevant to oncology.
  • To discuss their roles in DNA metabolism and potential as cancer drug targets.
  • To explore the progress and utility of targeting OB-folds in cancer therapy.

Main Methods:

  • Literature review focusing on OB-fold containing proteins in DNA metabolism.
  • Analysis of structural features of OB-fold motifs.
  • Discussion of current research on drugging OB-fold proteins for cancer treatment.

Main Results:

  • OB-fold motifs are key structural elements for DNA binding in proteins critical for genome maintenance.
  • Several OB-fold proteins are implicated in cancer development and progression.
  • Emerging strategies are targeting OB-fold containing proteins for therapeutic intervention.

Conclusions:

  • Targeting OB-fold proteins represents a developing frontier in cancer drug discovery.
  • Successful agents could offer new avenues for cancer treatment by modulating genome stability pathways.
  • Despite initial challenges, targeting protein-DNA interactions via OB-folds is increasingly feasible.
Keywords:
DNA bindingDNA damage responseDNA repairDNA replicationOB-foldcancer therapydrug developmentgenome stabilitysingle-stranded DNA

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