Download Bloom Helicase

Bloom Helicase
Sheena Cooper
BIOL 445
Spring 2013
Bloom Syndrome
http://med.cornell.edu/bsr/i/map.gif
Characterized by…
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Small stature
Eating problems
Skin changes
Immune deficiencies
Premature aging
COPD
Diabetes
Chromosomal instabilities =
CANCER
http://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
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
<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.