Bloom Helicase

Sheena CooperBIOL 445

Spring 2013

Bloom Syndrome

http://med.cornell.edu/bsr/i/map.gif

Characterized by…

• Small stature• Eating problems• Skin changes• Immune deficiencies• Premature aging• COPD• Diabetes• Chromosomal instabilities =

CANCERhttp://med.cornell.edu/bsr/clinical_description/

Diagnosis

Chaganti et al., PNAS, pg 4508, 1974

BLM

Monnat, Seminars in Cancer Biology, pg 329, 2010

RECQ family

• Includes five helicases• Three of these cause cancer predisposition

syndromes

Function in Cell

Monnat, Seminars in Cancer Biology, pg 329, 2010

Function in Organism

Mice and humans are a little different…

Monnat, Seminars in Cancer Biology, pg 329, 2010

BLM in cancer

Monnat, Seminars in Cancer Biology, pg 329, 2010

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

BLM inhibitors in treatment of non-BS cancers

Nguyen et al., Cell Press, pg 55, 2013

ReferencesA 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 <http://www.bloomssyndrome.org/bloomssyndrome.htm >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.