DNA repair and recombination is crucial for the fidelity of DNA replication. The RecQ family of DNA helicases is required for this process and in humans, mutations in these genes leads to the Bloom's, Werner's, and Rothmund-Thomson syndromes. All of these diseases are fundamentally characterized by a predisposition to cancer due to chromosomal loss and rearrangement. In yeast, the Sgs1 protein, is the only homologue to the human RecQ family of DNA helicases. Mutations in this protein recapitulate the affects observed with the human diseases suggesting that its functions have been conserved to humans. Due to the vast ease of doing genetics, cellular biology, and molecular biochemistry in yeast, this model organism is ideal to study this family of DNA helicases. Outlined here, I plan to further characterize the role of the Sgs1 protein in the DNA repair pathway and to find and characterize additional interacting proteins to Sgs1. Using techniques developed in the Rothstein laboratory, I will be able to further understand the mechanism of how the Sgs1 protein leads to cancer development in higher eukaryotes. ? ? ?
|Bernstein, Kara A; Mimitou, Eleni P; Mihalevic, Michael J et al. (2013) Resection activity of the Sgs1 helicase alters the affinity of DNA ends for homologous recombination proteins in Saccharomyces cerevisiae. Genetics 195:1241-51|
|Bernstein, Kara A; Juanchich, Amélie; Sunjevaric, Ivana et al. (2013) The Shu complex regulates Rad52 localization during rDNA repair. DNA Repair (Amst) 12:786-90|
|Bernstein, Kara A; Reid, Robert J D; Sunjevaric, Ivana et al. (2011) The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Mol Biol Cell 22:1599-607|
|Bernstein, Kara A; Gangloff, Serge; Rothstein, Rodney (2010) The RecQ DNA helicases in DNA repair. Annu Rev Genet 44:393-417|
|Bernstein, Kara A; Rothstein, Rodney (2009) At loose ends: resecting a double-strand break. Cell 137:807-10|
|Bernstein, Kara A; Shor, Erika; Sunjevaric, Ivana et al. (2009) Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair. EMBO J 28:915-25|