Onco, Tumor-Suppressor, and DNA Repair Genes

1. Onco, Tumor-Suppressor, and DNA Repair Genes Catherine Hanson Chelsea Harmon Abby Llaneza Jen Williams

3. Tumor Suppressor Genes • Normal Function • Inhibit or "put the brakes on" the cell growth and division cycle • They function to prevent the development of tumors • Abnormal Function • Mutations in tumor suppressor genes cause the cell to ignore one or more of the components of the network of inhibitory signals • Removing the brakes from the cell cycle and resulting in a higher rate of uncontrolled growth—cancer.

4. Example of Tumor Suppressor Gene • p53 • Involved in a wide range of tumors • Inactive or lost in more than 50% of cancerous cells • Codes for the cytoplasmic p53 protein that regulates cell division and can induce cells to kill themselves ( a.k.a. Apoptosis) • Inheritance of p53 mutations through the germ line is also associated with the Li-Fraumeni cancer syndrome

5. p53 Gene Structure

6. Tumor Suppression Table • This Table shows the Tumor Suppression by a Single Chromosome Transfer

7. Oncogenes • Oncogenes are mutated forms of proto-oncogenes, functions to encourage and promote normal growth and the division of cells. • When proto-oncogenes mutate to become carcinogenic oncogenes, the result is excessive cell multiplication. • Oncogene the word is derived from the Greek word "oncos," meaning tumor.

8. Examples of Oncogenes • erb-B • Codes for a receptor for epidermal growth factor • Involved in glioblastoma, a brain cancer, and breast cancer • erb-B2 • Also called HER-2 or neu • Involved in breast, ovarian, and salivary gland cancers • Ki-ras • Codes for a protein that relays a stimulatory signal • Involved in lung, ovarian, colon, and pancreatic cancers

9. Examples of Oncogenes, con’t • N-ras • Involved in leukemias • c-Myc, N-myc, L-myc • All genes for transcription factors that activate growth- promoting genes • Involved in leukemias, breast, stomach, and lung cancers (c-Myc, L-myc); neuroblastoma (N-myc) • Bcl-1 • Codes for cyclin D1, a component of the cell cycle clock • Involved in breast as well as head and neck cancers

10. DNA Repair Genes • Normally ensure that each strand of genetic information is accurately copied during cell division • Mutations in lead to an increase in the frequency of other mutations • Broken and/or fragmented chromosomes cause faulty repair enzymes • http://intouchlive.com/home/frames.htm?http://intouchlive.com/cancergenetics/dnafix.htm&3

11. Examples of DNA Damage • Loss of a base • Breaks in one of the DNA strands • Addition of methyl group to guanine • Thymine dimer formation (linkage of two adjacent thymine bases on one of the DNA strands)

12. ATM and NBS1 - DNA repair genes: • These proteins are involved in two genetic disorders that lead to an increased chance of breast cancer. These disorders are ataxia-telangiectasia and Nijmegen breakage syndrome. • ATM is the mutated protein in ataxia-telangiectasia, it is a kinase that regulates cell cycle checkpoints and is activated by DNA damage. NBS1 is the protein that impacts Nijmegen breakage syndrome. Similarly, this protein is also activated by DNA damage and this activation results in the protein repairing the broken strands of DNA.

13. ATM and NBS1 - DNA repair genes: (cont) • Recently, scientists found that these disorders are related. ATM, phosphorylates NBS1 at two sites on the DNA, and is required for the activation of NBS1 and the subsequent repair of damaged DNA. • This knowledge explains the similarites between the disorders and gives researchers a greater understanding of cancer growth patterns. • source: http://breastcancer.about.com/health/breastcancer/library/didyouknow/blak.htm?iam=dpile&terms=%2BDNA+%2Brepair+%2Bgene