Cancer & DNA Damage Summary

Objectives

• Understand chromosomal rearrangements from DNA double-strand breaks (DSBs) leading to cancer.
• Apply chromosomal rearrangements to gene regulation disruption.
• Examine examples of cancer hallmarks related to gene expression.
• Comprehend the DNA Damage Response (DDR) activation in G1/S and G2/M phases.
• Recognize the functions of key proteins in the DNA damage response and cell cycle regulation.

Cancer Statistics

• Approx. 2 million new cancer cases in the U.S. annually (2024).
• ~600,000 cancer deaths in the U.S. (2021).
• Cancer is the second leading cause of death in the U.S.

Key Cancer Types

• Common Cancers (2021 estimates):
  • Breast: 281,550 new cases; 43,600 deaths
  • Prostate: 248,530 new cases; 34,130 deaths
  • Lung: 116,660 new cases; 69,410 deaths
  • Colon: 104,270 new cases; 52,550 deaths

DNA Damage Response (DDR)

• DDR inhibits cyclin-CDK to prevent cell cycle progression when DNA is damaged.
• Key proteins include:
  • ATM: Senses DNA DSBs, activates repair pathways, phosphorylates targets like p53.
  • p53: A tumor suppressor that activates genes for cell cycle arrest.
• if damage is too severe, cells undergo apoptosis.

DNA Damage Checkpoints

• Ensures DNA damage is repaired before cell division:
  • G1/S checkpoint: Arrest if damage is present.
  • G2/M checkpoint: Similar function to prevent mitosis with damage.
• Importance of checkpoints in tumor suppression and cancer prevention.

Chromosomal Rearrangements

• Result from DNA damage can cause gene regulation changes.
• May involve deletions, inversions, or translocations influencing oncogenes/tumor suppressors.
• Cell-type specificity is crucial, as the effect of rearrangement varies by cell type.

Study Practices

• Understand the relationships between regulatory elements and transcription factors in specific cell types.
• Interpret diagrams related to DNA damage and cell cycle control.
• Recognize the role of miRNAs in protein regulation in the context of the DNA damage response.