Safeguarding chromosome structure: Double strand break repair

5 important questions on Safeguarding chromosome structure: Double strand break repair

How do aneuploidy and chromosome structures contribute to tumorigenesis?

  • Intratumor heterogeneity
  • Gain of oncogenes
  • Loss of tumor suppressor genes

How do these abnormal chromosome structures (acentric/dicentric) form?

Mainly by improper repair of DNA damage; double-strand breaks (DSBs)

What are the main exogenous causes of DSBs?

  1. Ionizing radiation
    • Gamma rays
    • X-ray
  2. Anti-cancer chemotherapeutics
    • DNA alkylating agents
    • DNA crosslinking agents
    • Topoisomerase inhibitors
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What are the main endogenous causes of DSBs?

  1. Metabolites (ROS, alkylating agents)
  2. V(D)J recombination (B and T-cells)
  3. Transcription (RNA:DNA hybrids)
  4. Replication stress
  5. Telomere dysfunction   

How do DSBs normally get repaired?

  1. Canonical DSB repair pathways
    • Non-Homologous End Joining (c-NHEJ)
    • Homologous Recombination (HR)
  2. Alternative DSB repair pathways
    • Single Strand Annealing (SSA)
    • Alternative End-Joining (alt-EJ)
    • Microhomology-mediated template switching     

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