I'm studying mechanisms that maintain genomic stability in S. cerevisiae. In particular, I'm analyzing how disruption of the topoisomerases Top1 and Top2 (by both mutation and by drug inhibition) induces mitotic DNA recombination. Top1 and Top2 are, respectively, important for transcription and chromosome segregation. These studies will give insights into how topoisomerase function is important for maintaining stable DNA during these processes. The drug studies are particularly interesting from a clinical viewpoint, as topoisomerase inhibitors are frequently used as chemotherapeutics, and this may be relevant to understanding the genome changes that result in chemotherapy-induced secondary cancers. I'm using high-throughput sequencing and SNP microarrays to fine map and characterize the recombination events. The project will also be extended into mammalian cells on a limited basis.

Public Health Relevance

Genome instability is associated with diseases such as cancer, and consequently studying the causes and effects of genome instability is important to human health. I am studying DNA topoisomerases, which are linked to both the induction of genome instability as well as protection from genome instability.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM100618-02
Application #
8515758
Study Section
Special Emphasis Panel (ZRG1-F08-E (20))
Program Officer
Janes, Daniel E
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Andersen, Sabrina L; Zhang, Aimee; Dominska, Margaret et al. (2016) High-Resolution Mapping of Homologous Recombination Events in rad3 Hyper-Recombination Mutants in Yeast. PLoS Genet 12:e1005938
Andersen, Sabrina L; Sloan, Roketa S; Petes, Thomas D et al. (2015) Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast. PLoS Genet 11:e1005098