DNA damage response mechanisms protect mammalian cells from genomic instability and phenotypes such as aging and cancer. In contrast to normal cells, tumors exhibit extreme genomic instability, which can occur at the level of DNA as well as at the chromosomal level. This course reviews the causes and consequences of genomic instability, including manifestations in DNA and chromosomes; the course also provides a thorough review of cellular DNA damage response mechanisms, including detection of damage, checkpoint signaling, and recruitment of repair factors.   

Learning Objectives

• List causes and consequences of genomic instability
• Define the following and explain their significance in cancer: chromosomal deletion, chromosomal translocation, chromosomal inversion, aneuploidy, polyploidy, internal tandem duplication and provide key examples
• Explain the difference between and the significance of somatic and germline mutations
• Describe the differences between single strand and double strand DNA breaks in terms of impact on the cell and repair processes involved
• Name the kinases involved in signaling for DNA damage Explain the following: mismatch repair, nucleotide excision repair, base excision repair, microsatellite instability. 
• Name cancers or cancer syndromes associated with deficiencies in these repair processes
• Recognize the key players in checkpoint signaling and DNA repair including the DNA damage response pathway components that are currently undergoing evaluation as therapeutic targets