Gene Ontology:
The Gene Ontology (GO) project refers to the work of many
researchers trying to create a database containing descriptions of genes over a
wide variety of organisms in a standardized manner [1]. The GO project
describes a gene product by using three different ontologies. The domains these
ontologies cover are Biological Process (BP) which refers to a set of events accomplished
by a series of molecular functions, Cellular Compartment (CC) which describes
the location of the gene product within the cell, and Molecular Function (MF)
which describes the activity the gene product is responsible for [2].
ATM Ontology:
Below are the three ontologies of the ATM protein which was retrieved from the GO website. They are split up into the three categories described above. ATM is a part of a wide variety of biological processes so they were divided into categories based on the general catagory the process was a part of.
Biological Process:
Development:
DNA Maintenance:
Cell Maintenance:
Other:
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Figure 1: This illustrates how DNA repair relates to other various biological processes. Moving from the bottom up the descriptions get more general.
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Cellular Component:
Cytoplasm
Nucleus
Spindle (Part of cytoskeleton)
Nucleus
Spindle (Part of cytoskeleton)
Figure 2: The ATM protein is known to be present in many parts of the cell. This chart refers to ATM being located in the nucleus.
Molecular Function:
Protein serine/threonine kinase activity
Figure 3: ATM is known to be a serine/threonine kinase and this gives a better description of what that really means. Again, going from bottom to top the descriptions get more general.
Discussion:
Based on the fact that ATM is a part of many biological processes, it is evident that it is an important gene. Given that it is involved in DNA and cell maintenance, it is not a surprise that mutations in the ATM gene leave a patient at risk for contracting Chronic Lymphocytic Leukemia or other lymphomas [3]. ATM’s role in the apoptotic pathway can also explain why CLL cells lacking a good copy of ATM do not respond normally to chemotherapeutics [4]. These drugs work to induce apoptosis to kill the cell, but if ATM is not present to participate in the pathway then the cancerous cell may ignore the death signal and continue to divide. The fact that ATM is involved in a wide variety of biological processes can also explain why CLL patients with an 11q- tend to have a poorer prognosis [5].
References:
1. Plessis, L. d., Škunca, N., & Dessimoz, C. (2011). The what, where, how and why of gene ontology—a primer for bioinformaticians. Oxford Jounrals, 12(6), 723- 735. doi:10.1093/bib/bbr002
2. Ashburner , M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., . . . Sherlock, G. (2000). Gene Ontology: tool for the unification of biology. Nature Genetics, 25(1), 25-29. doi:10.1038/75556
3. McKinnon, P. (2004). ATM and ataxia telangiectasia. EMBO reprots, 5(8), 772-776. doi:10.1038/sj.embor.7400210
4. Austen, B., Skowronska, A., Baker, C., Powell, J. E., Gardiner, A., Oscier, D., . . . Stankovic, T. (2007). Mutation Status of the Residual ATM Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion. Journal of Clincial Oncology, 25(34), 5448-5457. doi:10.1200/JCO.2007.11.2649
5. Kalil, N., & Cheson, B. (1999). Chronic Lymphocytic Leukemia. The Oncologist, 4(5), 352-369. Retrieved from http://theoncologist.alphamedpress.org/content/4/5/352.short
2. Ashburner , M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., . . . Sherlock, G. (2000). Gene Ontology: tool for the unification of biology. Nature Genetics, 25(1), 25-29. doi:10.1038/75556
3. McKinnon, P. (2004). ATM and ataxia telangiectasia. EMBO reprots, 5(8), 772-776. doi:10.1038/sj.embor.7400210
4. Austen, B., Skowronska, A., Baker, C., Powell, J. E., Gardiner, A., Oscier, D., . . . Stankovic, T. (2007). Mutation Status of the Residual ATM Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion. Journal of Clincial Oncology, 25(34), 5448-5457. doi:10.1200/JCO.2007.11.2649
5. Kalil, N., & Cheson, B. (1999). Chronic Lymphocytic Leukemia. The Oncologist, 4(5), 352-369. Retrieved from http://theoncologist.alphamedpress.org/content/4/5/352.short
This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison