1. Bloom Helicase Sheena Cooper BIOL 445 Spring 2013

2. Bloom Syndrome http://med.cornell.edu/bsr/i/map.gif

3. Characterized by… Small stature Eating problems Skin changes Immune deficiencies Premature aging COPD Diabetes Chromosomal instabilities = CANCER http://med.cornell.edu/bsr/clinical_description/

4. Diagnosis Chaganti et al., PNAS, pg 4508, 1974

5. BLM Monnat, Seminars in Cancer Biology, pg 329, 2010

6. RECQ family Includes five helicases Three of these cause cancer predisposition syndromes

7. Function in Cell Monnat, Seminars in Cancer Biology, pg 329, 2010

8. Function in Organism Mice and humans are a little different… Monnat, Seminars in Cancer Biology, pg 329, 2010

9. BLM in cancer Monnat, Seminars in Cancer Biology, pg 329, 2010

10. Treatment of BS No real treatment—just management of symptoms related to infections, diabetes, and eating problems as well as early screenings for various types of cancers

11. BLM inhibitors in treatment of non-BS cancers Nguyen et al., Cell Press, pg 55, 2013

12. References A Concise Clinical Description of Bloom’s Syndrome. Retrieved from http://med.cormell.edu/bsr/clinical_description/ Banerjee, T. (2013). A new development in DNA repair modulation: Discovery of a BLM helicase inhibitor. Cell Cycle, 12(5), 713-714. Chaganti, R. S. K., et al. (1974). A Manyfold Increase in Sister Chromatid Exchanges in Bloom's Syndrome Lymphocytes. Proceedings of the National Academy of Sciences, 71(11), 4508-4512. German, J. Bloom's syndrome. Retrieved from Gyimesi, M., et al. (2012). Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains. Nucleic Acids Research, 40(9), 3952-3963. Mirzaei, H. (2012). Non-bloom syndrome-associated partial and total loss-of-function variants of BLM helicase. Proceedings of the National Academy of Sciences, 109(47), 19357-19362. Monnat Jr., R. J. (2010). Human RECQ helicase: Roles in DNA metabolism, mutagenesis and cancer biology. Seminars in Cancer Biology, 329-339. Nguyen, G., et al. (2013). A Small Molecule Inhibitor of the BLM Helicase Modulates Chromosome Stability in Human Cells. Cell Press, 20, 55-62. Wan, L., et al. (2013). Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proceedings of the National Academy of Sciences.