Assistant Professor, Department of Pediatrics - Hematology/Oncology and Department of Molecular and Human Genetics

B.S. (Biology), Massachusetts Institute of Technology, Cambridge, MA, 1981-1985
M.S., M.D., and Ph.D. (Biology), University of Rochester, NY, 1985-1993
Internship, Pediatrics, Baylor College of Medicine, 1993-1994
Residency, Pediatrics, Baylor College of Medicine, 1994-1996
Clinical Fellowship, Pediatric Hematology and Oncology, Baylor College of Medicine, 1996-1999
Postdoctoral Training, Baylor College of Medicine, 1997-2003

RESEARCH INTERESTS:

My laboratory is interested in the mechanisms by which cells differentiate natural chromosome termini from DNA ends created by double-strand breaks (DSBs). DSBs present a significant threat to genome integrity because of the permanent cell cycle arrest or cell death they induce if left unrepaired. Consequently, organisms have evolved complex mechanisms to efficiently respond to and repair chromosomal DSBs. Natural chromosome termini, on the other hand, must be protected at least to some extent from these same pathways in order to prevent the fusion of chromosome ends or other detrimental outcomes. This is achieved through the specialized nucleoprotein structures known as telomeres. Paradoxically, many activities that function in the response to DSBs also have roles in normal telomere structure, function, and maintenance.

The Ku heterodimer is one such protein with dual roles at broken and telomeric ends. Ku is a high affinity DNA end binding complex critical for DNA DSB repair via nonhomologous end joining (NHEJ) and, surprisingly, multiple aspects of telomere biology. Previous work by us and others has firmly established that Ku performs separable activities at DSBs versus telomeres, however the mechanisms of action at these sites have yet to be fully elucidated. Ku is also a principal mediator of the catastrophic end-to-end fusions that can occur at dysfunctional telomeres. How Ku’s NHEJ activity is inhibited at wild type telomeres remains poorly defined. We are pursuing the answers to these questions in Saccharomyces cerevisiae, a genetically tractable model organism, which has contributed greatly to our current understanding of telomere biology and DNA DSB repair. Most recently, as a result of a comprehensive site-directed mutagenesis of the yeast Ku70 and Ku80 subunit genes, we have proposed a ‘two-face’ model for Ku’s functions at DSBs versus telomeres - whereby there is an outward face that mediates NHEJ and an inward face that mediates Ku’s telomeric functions. Our current work seeks to test and expand various aspects of this model and to elucidate the molecular determinants of Ku’s ability to protect telomeric ends from aberrant repair activities.

In addition, my laboratory is interested in the role of telomere dysfunction in the malignant bone tumor osteosarcoma. For example, we are examining whether loss of telomere end protection contributes to genome instability in osteosarcoma. In addition, we are pursuing the factors that govern telomere maintenance in this malignancy. In stark contrast epithelial cancers, which generally re-activate the telomere-replication enzyme, telomerase, in order to maintain their telomeres, osteosarcomas frequently utilize a pathway known as ALT (for alternative lengthening of telomeres), which remains poorly defined. By elucidating the principal components of this pathway, we hope to identify novel targets for osteosarcoma treatment.

SELECTED PUBLICATIONS:

1. Ribes-Zamora A, Mihalek I, Lichtarge O, Bertuch AA (2007). Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nature Struct. Mol. Biol. 14: 301-307.

2. Bertuch AA, Lundblad V (2006). The maintenance and masking of chromosome termini. Curr. Opin. Cell Biol. 18: 247-253.

3. Hermanns P, Bertuch AA, Bertin T, Dawson B, Schmitt ME, Zabel B, Lee B (2005). Consequences of mutations in the noncoding RMRP RNA in the pathogenesis of Cartilage-Hair Hypoplasia. Hum. Mol. Genet. 14: 3723-3740.

4. Bertuch AA, Lundblad V (2004). EXO1 contributes to telomere maintenance in both telomerase-proficient and telomerase-deficient Saccharomyces cerevisiae. Genetics 166: 1651-1659.

5. Bertuch AA, Lundblad V (2003). The Ku heterodimer performs separable activities at double strand breaks and chromosome termini. Mol. Cell. Biol. 23: 8202-8215

6. Bertuch AA, Lundblad V (2003). Which end: dissecting Ku's function at telomeres and double-strand breaks. Genes Dev. 17: 2347-2350.

7. Bertuch AA, Buckley K, Lundblad V (2003). The way to the end matters: the role of telomerase in tumor progression. Cell Cycle 2: 36-38.

8. Bertuch AA (2002). When ends meet: The molecular events driving telomeric fusions. Curr. Biol. 12: R738-40.

9. Evans SK, Bertuch AA, Lundblad V (1999). Telomeres and telomerase: at the end it all comes together. Trends Cell Biol. 9: 329-331.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Alison A. Bertuch, M.D., Ph.D.
Texas Children’s Hospital
Texas Children’s Cancer Center
Feigin Center , Room 1240.08
1102 Bates, MC 3-3320
Houston , TX 77030
Mail Stop: BCM320

Phone: 832-824-4579
Fax: 832-825-4651
E-mail:

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